Enfortumab Vedotin-Induced Febrile Neutropenia and Hyperglycemia Successfully Treated with Multidisciplinary Treatment Including Continuous Hemodialysis Filtration and Insulin Injection in a Patient with Chemo-Resistant Metastatic Urothelial Carcinoma: A Case Report.

Introduction: Enfortumab vedotin (EV) is an antibody-drug conjugate combining a monoclonal antibody targeting nectin-4 with a highly potent microtubule disrupting agent. EV is expected to be a candidate for the third-line treatment for urothelial carcinoma previously treated with platinum-based chemotherapy and PD-1/PD-L1 inhibitors. Very few cases of patients experienced hyperglycemia of unknown cause. Case Presentation: We describe a 72-year-old Asian man with mild obesity, type 2 diabetes, hyperlipidemia, hypertension, and chemo-resistant metastatic urothelial carcinoma. He developed hyperglycemia and febrile neutropenia after 3 doses of EV. He had hyperglycemia of 489 mg/dL and was started on continuous intravenous insulin infusion (CVII). The patient's intravenous insulin requirements peaked at 316 units per day. He also developed febrile neutropenia and consequent sepsis caused acute kidney injury. Continuous hemodialysis filtration (CHDF) together with antibiotics were started to treat the septic condition. The blood glucose level gradually decreased after CHDF treatment and CHDF was continued for 14 days. The timing of liberation from CHDF correlated with the elimination half-life of EV of 3.4 days. CVII was treated for 26 days and the patient was finally released from the intensive care unit. Conclusion: This case indicates that the uncontrollable hyperglycemia induced by EV during metastatic urothelial carcinoma treatment is effectively managed with CVII and CHDF until the elimination of the adverse effect of EV.

Amyloidoma: A Case Report of Remote Insulin-Derived Amyloidosis in the Setting of Insulin-Dependent Diabetes.

The incidence of insulin-induced amyloidosis distant from an injection site is unknown. Due to its rare nature, only a few case reports have been reported, with even fewer describing amyloidoma as distant from the insulin injection site. We present a case of a 52-year-old male with a left arm mass that was determined to be cutaneous amyloidosis and successfully treated with total excision of the mass. Histopathological examination with Congo red stain demonstrated classic characteristics of amyloidosis. We present this case report to increase awareness of this relatively rare occurrence.

MDI versus CSII in Chinese adults with type 1 diabetes in a real-world situation: based on propensity score matching method.

BACKGROUND: Compared with multiple daily insulin injections (MDI), continuous subcutaneous insulin infusion (CSII) is significantly more expensive and has not been widely used in Chinese type 1 diabetes mellitus (T1DM) patients. So there are still significant knowledge gaps regarding clinical and patient-reported outcomes in China. AIMS: This study aims to compare the glycated hemoglobin (HbA1C), insulin therapy related quality of life (ITR-QOL), fear of hypoglycemia (FOH) of adult T1DM patients treated with MDI and CSII based on propensity score matching in real-world conditions in China. METHODS: Four hundred twenty adult T1DM patients who were treated with MDI or CSII continuously for more than 12 months in a national metabolic center from June 2021 to June 2023 were selected as the study subjects. Their QOL and FOH were evaluated with Insulin Therapy Related Quality of Life Measure Questionnaire-Chinese version (ITR-QOL-CV) and the Chinese Version Hypoglycemia Fear Survey-Worry Scale (CHFSII-WS), and their HbA1C were collected at the same time. Potential confounding variables between the two groups were matched using propensity score matching. RESULTS: Of the 420 patients included in the study, 315 were in MDI group and 105 were in CSII group. 102 pairs were successfully matched. After matching, the total score of ITR-QOL-CV scale in CSII group was significantly higher than that in MDI group (87.08 ± 13.53 vs. 80.66 ± 19.25, P = 0.006). Among them, the dimensions of daily life, social life, and psychological state were all statistically different (P < 0.05). The scores of CHFSII-WS (8.33 ± 3.49 vs. 11.77 ± 5.27, P = 0.003) and HbA1C (7.19 ± 1.33% vs. 7.71 ± 1.93%, P = 0.045) in CSII group were lower than those in MDI group. CONCLUSIONS: 25.0% of T1DM adults are treated with CSII. Compared with adult T1DM patients treated with MDI, those treated with CSII have higher ITR-QOL, less FoH, and better control of HbA1C in real-world conditions in China. Therefore, regardless of economic factors, CSII is recommended for adult T1DM patients to optimize the therapeutic effect and outcomes.

Predictive value of postprandial C-peptide for utilizing multiple daily injection therapy in type 2 diabetes.

PURPOSE: Multiple daily injection (MDI) insulin therapy is an effective method of glycemic control and appropriate assignment to MDI therapy could minimize the risks of hypoglycemia and weight gain. The aim of the present study was to identify factors associated with indication for MDI therapy in type 2 diabetes (T2DM). METHODS: We recruited 360 participants with T2DM that were admitted to the Endocrinology Department of Peking University People's Hospital between August 2017 and July 2018. They first underwent intensive insulin therapy, then were switched to an optimized, simpler insulin treatment that aimed to maintain fasting blood glucose between 4.4 and 7.2 mmol/L, without episodes of hypoglycemia. The baseline characteristics of groups administering either MDI or basal/premix insulin were compared and multivariable logistic regression analysis was used to determine the odds ratios (ORs) for factors associated with MDI therapy. Receiver operating characteristic (ROC) curves were then used to identify independent predictors of MDI insulin regimen efficacy. RESULTS: The mean age of the participants was 57.6 ± 12.9 years, and diabetes duration was 14.2 ± 8.2 years. Two hundred and sixty-seven participants administered basal/premix insulin and 93 underwent MDI therapy, of whom 61.8% and 46.2% were male, respectively (p = 0.01). The duration of diabetes was significantly longer in the MDI group (13.1 ± 7.7 years vs. 17.3 ± 8.7 years; p < 0.01). Fasting plasma glucose (FPG) was higher in the MDI group than in the basal/premix group (8.3 [6.7, 11.3] mmol/L vs. 7.2 [5.7, 9.3] mmol/L; p < 0.01), while the postprandial C-peptide concentration (PCP) was significantly lower in the MDI group (2.6 [1.8, 3.5] ng/mL) compared to the basal/premix group (3.6 [2.5, 6.2] ng/mL, p < 0.01. Multivariable logistic regression analysis suggested that diabetes duration and FPG were positively associated with MDI therapy: OR (95% confidence interval [CI]) 1.06 (1.02, 1.10) and 1.12 (1.02, 1.24), respectively. In addition, PCP was negatively associated with MDI therapy (0.72 [0.60, 0.86]). ROC analysis suggested that a PCP of < 3.1 ng/mL predicted MDI therapy with 59.6% sensitivity and 72.1% specificity. CONCLUSION: The results of our study suggest that longer diabetes duration, higher FPG, and lower PCP were associated with necessity for MDI insulin regimen. These findings should assist with the personalization of insulin treatment.

Differences in clinicopathological characteristics between lipohypertrophy and localized insulin-derived amyloidosis: A scoping review.

Insulin is used as a therapeutic agent in patients with diabetes, and cutaneous lipohypertrophy (LH) and localized insulin-derived amyloidosis (LIDA) are well-known adverse effects associated with insulin injections. The clinical implications, management, assessment methods, and pathological differentiation of LH and LIDA have been recently updated. This review was to update our knowledge of the pathological differentiation, effects of insulin absorption, hypoglycemic events, and recent assessment methods for LH and LIDA. A scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews guidelines. Original studies and case reports in English were also included. PubMed and Scopus databases were searched for keywords to identify papers published up to January 2022. A total of 113 studies were identified through a database search, and 31 were eligible for inclusion in this scoping review. In the 31 studies included in this review, patients with type 2 diabetes had high frequencies of LH and LIDA. LH outcome parameters were assessed using pathological findings and imaging. LIDA is mainly determined by pathological methods, such as hematoxylin and eosin and Congo red staining. Several in vitro and in vivo LIDA models of LIDA have been developed. These results suggest that pathological analysis is required to identify LH and LIDA. It is important to consider LIDA, as it likely influences insulin adsorption and glycemic control. Although several studies have evaluated the LIDA process, little is known about the mechanisms underlying the development of adverse effects associated with insulin injections.

Exploring the Diagnostic Value of High-Frequency Ultrasound Technology for Subcutaneous Lipohypertrophy in Diabetes Patients Receiving Insulin Injections.

Objective: This study aims to investigate the clinical application value of high-frequency ultrasound technology in diagnosing subcutaneous lipohypertrophy at insulin injection sites in diabetes patients. Methods: All diabetes patients treated in our hospital from January 2022 to January 2023 were selected as the study subjects. The incidence of subcutaneous lipohypertrophy was calculated at the end of the study period. All patients were screened, and those meeting the inclusion criteria were registered, and basic data were collected. Patients were screened for subcutaneous lipohypertrophy using conventional clinical examination (control group) and high-frequency ultrasound technology (study group). Results: The study found that the incidence of subcutaneous lipohypertrophy in diabetes patients receiving insulin injections in our hospital from January 2022 to January 2023 was 80.99%. The average longitudinal diameter of subcutaneous lipohypertrophy in these patients was 11.66 (7.56, 21.44) mm, the transverse diameter was 12.04 (8.96, 18.29) mm, depth was (5.62±2.17) mm, and the area was 188.79 (76.85, 331.78) mm². The clinical detection rate in the study group was higher than that in the control group (P<0.05). The quantity of detected sites was greater in the study group compared to the control group (P<0.05). Conclusion: The incidence of subcutaneous lipohypertrophy in diabetes patients receiving insulin injections is relatively high clinically, and high-frequency ultrasound technology demonstrates significant potential in diagnosis. By providing high-resolution imaging and quantitative data, it effectively improves the clinical detection rate and clarifies symptoms. This technology is likely to become an important auxiliary tool in future diabetes treatment, providing more precise treatment plans for patients.

Are People With Type 1 Diabetes Mellitus Appropriately Following Insulin Injection Technique Practices: A Review of Literature.

People with type 1 diabetes mellitus (T1DM) need to take multiple doses of insulin injections daily throughout their lives. However, a notable portion of people with diabetes mellitus (DM) show suboptimal insulin injection technique practices. They are supposed to follow the recommended insulin injection technique guidelines. Our explorative literature search, including studies from the past 30 years, is expected to identify the deficiencies of self-injection insulin techniques and the associated complications in people with T1DM, where we have summarised the overall incidence of complications that have occurred due to nonadherence of the prescribed guidelines, along with their associated risk factors. We have attempted to include multiple systematic reviews, meta-analyses, literature reviews, case reports, and original articles from the search engines and databases like PubMed, Scopus, ScienceDirect, Cochrane Library, Google Scholar, and BioMed Central, and studies with only human participants were included in this search. The knowledge sharing from this research may be utilised for enhancing the structured education diabetes programme and implementing the population-based corrective measures, including the thrust areas in future multi-centre longitudinal research studies and recommendations, which can prevent unnecessary complications and enhance their quality of life. Correct insulin administration technique, abstaining from administration of injection at the areas with lipohypertrophy, rotation of injection sites, and ultrasound scanning can be used as a complimentary method to detect the lipohypertrophy at an early stage. Liposuction is beneficial in reducing the extensive lipohypertrophic tissues but helps achieve only cosmetically satisfactory outcome; thus, empowering people to follow insulin injection technique guidelines is one of the best strategies to reduce the high prevalence of lipohypertrophy. To conclude, education among the people with DM, especially T1DM who have to take insulin regularly, needs to be carried out consistently in the clinical settings, to prevent the severe complications caused due to inappropriate insulin injection techniques.

Insulin pump treatment vs. multiple daily insulin injections in patients with poorly controlled Type 2 diabetes mellitus: a comparison of cardiovascular effects.

AIMS: Both hyperglycaemia and large glycaemic variability are associated with worse outcomes in patients with Type 2 diabetes mellitus (T2DM), possibly causing sympatho-vagal imbalance and endothelial dysfunction. Continuous subcutaneous insulin injection (CSII) improves glycemic control compared to multiple daily insulin injections (MDI). We aimed to assess whether CSII may improve cardiac autonomic and vascular dilation function compared to MDI. METHODS: We enrolled T2DM patients without cardiovascular disease with poor glycaemic control, despite optimized MDI therapy. Patients were randomized to continue MDI (with multiple daily peripheral glucose measurements) or CSII; insulin dose was adjusted to achieve optimal target ranges of blood glucose levels. Patients were studied at baseline and after 6 months by: 1) flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial artery; 2) heart rate variability (HRV) by 24-hour ECG Holter monitoring (HM). 7-day continuous glucose monitoring (CGM) was performed in 9 and 8 patients of Group 1 and 2, respectively. RESULTS: Overall, 21 patients were enrolled, 12 randomized to CSII (Group 1) and 9 to MDI (Group 2). The daily dose of insulin and Hb1AC did not differ significantly between the 2 groups, both at baseline and at follow-up. Glucose variability showed some significant improvement at follow-up in the whole population, but no differences were observed between the 2 groups. Both FMD and NMD, as well as HRV parameters, showed no significant differences between the 2 groups at 6-month follow-up. CONCLUSIONS: In this randomized small study we show that, in T2DM patients, CSII achieves a similar medium-term glycemic control compared to MDI, without any adverse effect on the cardiovascular system.

Relationship Between Lipohypertrophy, Glycemic Control, and Insulin Dosing: A Systematic Meta-Analysis.

Background: Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects diabetes management. Our study aimed to assess the potential correlation between lipohypertrophy and glycemic control, as well as insulin dosing in patients with diabetes. Methods: We performed a systematic review followed by a meta-analysis to collect data about glycemic control and insulin dosing in diabetic patients with and without lipohypertrophy. To identify relevant studies published in English, we searched medical databases (MEDLINE/PubMed, Embase, and CENTRAL) from 1990 to January 20, 2023. An additional hand-search of references was performed to retrieve publications not indexed in medical databases. Results of meta-analyses were presented either as prevalence odds ratios (pORs) or mean differences (MDs) with 95% confidence intervals (95% CIs). This study was registered on PROSPERO (CRD42023393103). Results: Of the 5540 records and 240 full-text articles screened, 37 studies fulfilled the prespecified inclusion criteria. Performed meta-analyses showed that patients with lipohypertrophy compared with those without lipohypertrophy were more likely to experience unexplained hypoglycemia (pOR [95% CI] = 6.98 [3.30-14.77]), overall hypoglycemia (pOR [95% CI] = 6.65 [1.37-32.36]), and glycemic variability (pOR [95% CI] = 5.24 [2.68-10.23]). Patients with lipohypertrophy also had higher HbA1c (MD [95% CI] = 0.55 [0.23-0.87] %), and increased daily insulin consumption (MD [95% CI] = 7.68 IU [5.31-10.06]). Conclusions: These results suggest that overall glycemic control is worse in patients with lipohypertrophy than in those without this condition.

Establishment of a safe disposal management program for home used sharp wastes from insulin injection among diabetic patients / 现代临床护理

Objective To establish a safe disposal management program for home used sharps waste of insulin injection so as to provide a reference for the standardised management of sharps waste after insulin.injection.Methods Based on the model of information-motivation-behavioural skills,the safe disposal management program for insulin needles used at home was developed by literature reviews and semi-structured interviews to investigate the perceptions and requirements of patients.The program was then modified and refined by two rounds of expert consultation with Delphi method.Results The effective retrieval rates of questionnaire for two rounds of expert consultations were 88.89%and 93.75%,with an expert authority coefficient at 0.93.In the second round,the mean importance scores of the items were 4.40 to 5.00,with a coefficient of variation ranged from 0 to 0.168.The established program consisted of three primary items,six secondary items,and 20 tertiary items.Conclusion The safe disposal management program for home used sharps waste of insulin injection established from the perspectives of information,motivation and behavioural skills was scientific and practical,which offered a guidance to healthcare professionals in the clinical practices.

Perceived School Experience of Children and Adolescents With Type 1 Diabetes in the Kingdom of Saudi Arabia.

BACKGROUND AND OBJECTIVE: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children globally affecting more than 1.2 million children worldwide. It is challenging to manage in children and adolescents, as it can have much more serious psychosocial impacts in these groups. The objective of this study was to investigate the perceived experience of children and adolescents with T1DM regarding the management of their condition while in school. METHODS:  We used a cross-sectional study design with descriptive statistics and non-probability consecutive sampling in this work. This study was conducted at the Department of Pediatrics, Qassim Armed Forces Hospital, Al-Qassim, Saudi Arabia, from July 2018 to December 2018. In this study, we included 84 school-aged children and adolescents from various schools in the Qassim region of the Kingdom of Saudi Arabia who had T1DM and met the inclusion criteria. After we obtained written informed consent from the participants, they filled out a survey questionnaire about their perceived school experience while being a T1DM patient. RESULTS:  Although most of the children believed that they were not prevented from managing their diabetes at school, most also believed that school personnel did not have adequate knowledge about diabetes. CONCLUSION:  In this study, adolescents and children with T1DM had mixed perceptions of their experience at school.

Impact of the Number of Needle Tip Bevels on the Exerted Forces and Energy in Insulin Pen Injections.

Patients affected with type 1 diabetes and a non-negligible number of patients with type 2 diabetes are insulin dependent. Both the injection technique and the choice of the most suitable needle are fundamental for allowing them to have a good injection experience. The needles may differ in several parameters, from the length and diameter, up to the forces required to perform the injection and to some geometrical parameters of the needle tip (e.g., number of facets or bevels). The aim of the research is to investigate whether an increased number of bevels could decrease forces and energy involved in the insertion-extraction cycle, thus potentially allowing patients to experience lower pain. Two needle variants, namely, 31 G × 5 mm and 32 G × 4 mm, are considered, and experimental tests are carried out to compare 3-bevels with 5-bevels needles for both the variants. The analysis of the forces and energy for both variants show that the needles with 5 bevels require a statistically significant lower drag or sliding force (p-value = 0.040 for the 31 G × 5 mm needle and p-value < 0.001 for 32 G × 4 mm), extraction force (p-value < 0.001 for both variants), and energy (p-value < 0.001 for both variants) during the insertion-extraction cycle. As a result, 3-bevels needles do not have the same functionality of 5-bevels needles, show lower capacity of drag and extraction, and can potentially be related to more painful injection experience for patients.

Improving insulin self-injection accuracy in patients with diabetes mellitus through a nursing project.

BACKGROUND: Non-standardized insulin injection has an impact on the efficacy of glucose control. OBJECTIVES: The aim of the study was to explore the effectiveness of a nursing project in improving the insulin self-injection accuracy of diabetes mellitus patients. MATERIAL AND METHODS: A total of 200 type 2 diabetes patients who received insulin therapy with an insulin pen were recruited at the First Affiliated Hospital of Army Medical University (Chongqing, China). Patients were randomly assigned to a control (n = 100) or intervention (n = 100) group. Conventional health education was conducted in the control group, while a nursing project and conventional health education were undertaken in the intervention group. The following parameters were analyzed between the 2 groups: standardized insulin pen use at admission and discharge, glycosylated hemoglobin (HbA1c), time in range (TIR), and adipose hyperplasia incidence rate 6 months after discharge. RESULTS: Concerning standardized insulin self-injection, the intervention group was superior to the control group, and the difference between the 2 groups was statistically significant (p < 0.05). The HbA1c levels (p = 0.000), TIR (p = 0.005) and adipose hyperplasia incidence rate 6 months after discharge (p = 0.000) all improved in the intervention group compared to the control group. CONCLUSIONS: The application of the nursing project effectively improved the efficacy of glucose control in diabetes mellitus patients.

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

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: Type 1 diabetes in pregnancy was less controllable and increased neonatal birth weight and neonatal hypoglycemia within 2 h 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. CONCLUSION: 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.

BACKGROUND: Pain and fear associated with insulin injections can cause children with type 1 diabetes mellitus to avoid insulin injections and skip doses. OBJECTIVE: To evaluate and compare pain and fear levels in children aged 6-12 years receiving subcutaneous insulin injection using the manual pressure and ShotBlocker methods. METHODS: A 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. RESULTS: All 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). CONCLUSION: Manual 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 PRACTICE: Both 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.

Needlestick Injuries With Insulin Injections: Risk Factors, Concerns, and Implications of the Use of Safety Pen Needles in the Asia-Pacific Region.

Globally, health care workers (HCWs) are at a high risk of occupational exposure to needlestick injuries (NSIs). Needlestick injuries not only are associated with an increased risk of infections caused by bloodborne pathogens but are also a primary source of emotional distress and job burnout for HCWs and patients. Insulin injection-related NSIs are common among HCWs working in hospitals in the Asia-Pacific (APAC) region and impose a significant burden. Insulin pen needles have a high risk of transmitting infections (at both the patient-end and cartridge end of the sharp) after use. Recapping a needle after administering an insulin injection poses a major risk to HCWs. Currently, several safety-engineered needle devices (SENDs) are available with active or passive safety mechanisms. Passive insulin safety pen needles with dual-ended protection and automatic recapping capabilities have resulted in a significant drop in accidental punctures to HCWs while administering insulin to patients with diabetes. In this article, we have reviewed the burden and common causes of NSIs with insulin injections among HCWs in the APAC region. We have discussed current approaches to address the issues associated with NSIs and the benefits of introducing SENDs in health care settings, including long-term care facilities, nursing homes, and home care settings where patients may require assisted insulin injections. This review also summarizes key strategies/recommendations to prevent NSIs in HCWs and patients with diabetes in the APAC region.

A Scientometric Analysis and Visualization of Scientific Research and Technology Innovation in Needle-free Insulin Injection From 1974 to 2022.

PURPOSE: Needle-free jet injection has to some extent improved the quality of life of patients with diabetes, but it has not been widely used. Therefore, we analyzed articles, clinical trials, and patents of needle-free insulin injection to (1) perform a systematic and comprehensive analysis of scientific research and technology innovation in needle-free insulin injection during the past 49 years (1974 to 2022) and (2) identify the status of scientific research and technology innovation, their limitations, and future trends. METHODS: With a new perspective, we use scientometric tools, including co-word and word frequency analyses, text mining, and cluster network analysis, to provide a scientometric analysis and visualization of articles, clinical trials, and patents related to needle-free insulin injection delivery applications. FINDINGS: Patent innovation in this field was more active than clinical research, and clinical research prevailed over basic research. Basic research and clinical trials in this field mainly involved therapy, penetration, tolerability, absorption, and pharmacokinetic properties. Drive mechanisms and needle-free injection devices were the core patent technologies in this field. IMPLICATIONS: Although needle-free insulin injection has been under development for decades, its full potential has not yet been reached; needle-free injection technology is still in the growth stage. The field of needleless insulin injection is dominated by patent technology innovation.

Non-severe hypoglycemia in type 1 diabetes: a randomized crossover trial comparing two quantities of oral carbohydrates at different insulin-induced hypoglycemia ranges.

Aims: Non-severe hypoglycemia (NS-H) is challenging for people living with type 1 diabetes (PWT1D) and often results from relative iatrogenic hyper-insulinemia. Current guidelines recommend a one-size-fits-all approach of 15-20 g of simple carbohydrates (CHO) every 15 min regardless of the triggering conditions of the NS-H event. We aimed to test different amounts of CHO to treat insulin-induced NS-H at various glucose ranges. Methods: This is a randomized, four-way, crossover study involving PWT1D, testing NS-H treatment outcomes with 16 g vs. 32 g CHO at two plasma glucose (PG) ranges: A: 3.0-3.5 mmol/L and B: <3.0 mmol/L. Across all study arms, participants consumed an additional 16 g of CHO if PG was still <3.0 mmol/L at 15 min and <4.0 mmol/L at 45 min post-initial treatment. Subcutaneous insulin was used in a fasting state to induce NS-H. Participants had frequent venous sampling of PG, insulin, and glucagon levels. Results: Participants (n = 32; 56% female participants) had a mean (SD) age of 46.1 (17.1) years, had HbA1c at 54.0 (6.8 mmol/mol) [7.1% (0.9%)], and had a diabetes duration of 27.5 (17.0) years; 56% were insulin pump users. We compared NS-H correction parameters between 16 g and 32 g of CHO for range A, 3.0-3.5 mmol/L (n = 32), and range B, <3.0 mmol/L (n = 29). Change in PG at 15 min for A: 0.1 (0.8) mmol/L vs. 0.6 (0.9) mmol/L, p = 0.02; and for B: 0.8 (0.9) mmol/L vs. 0.8 (1.0) mmol/L, p = 1.0. Percentage of participants with corrected episodes at 15 min: (A) 19% vs. 47%, p = 0.09; (B) 21% vs. 24%, p = 1.0. A second treatment was necessary in (A) 50% vs. 15% of participants, p = 0.001; (B) 45% vs. 34% of participants, p = 0.37. No statistically significant differences in insulin and glucagon parameters were observed. Conclusions: NS-H, in the context of hyper-insulinemia, is difficult to treat in PWT1D. Initial consumption of 32 g of CHO revealed some advantages at the 3.0-3.5 mmol/L range. This was not reproduced at lower PG ranges since participants needed additional CHO regardless of the amount of initial consumption. Clinical trial registration: ClinicalTrials.gov, identifier NCT03489967.

Assessing Barriers and Adherence to Insulin Injection Technique in People With Diabetes: Development and Validation of New Assessment Tools.

BACKGROUND: The correct injection technique is crucial for people with insulin therapy. However, barriers to insulin injections exist, which can lead to problems with injections. In addition, injection behavior may deviate from recommendations leading to lower adherence to the correct injection technique. We developed two scales to assess barriers and adherence to the correct technique. METHODS: Two item pools were created to assess barriers to insulin injections (barriers scale) and adherence to the correct technique (adherence scale). In an evaluation study, participants completed the two newly created scales, as well as other questionnaires used for criterion validity. Exploratory factor analysis, correlational analysis, and receiver operating characteristics analysis were computed to analyze the validity of the scales. RESULTS: A total of 313 people with type 1 and type 2 diabetes using an insulin pen for insulin injections participated. For the barriers scale, 12 items were selected achieving a reliability of 0.74. The factor analysis revealed three factors namely emotional, cognitive, and behavioral barriers. For the adherence scale, nine items were selected achieving a reliability of 0.78. Both scales showed significant associations with diabetes self-management, diabetes distress, diabetes acceptance, and diabetes empowerment. Receiver operating characteristics analysis showed significant area under the curves for both scales in classifying people with current skin irritations. CONCLUSIONS: Reliability and validity of the two scales assessing barriers and adherence to insulin injection technique were demonstrated. The two scales can be used in clinical practice to identify persons in need of education in insulin injection technique.

Insulin injection practice and health related quality of life among individuals with diabetes at Tikur Anbessa Specialized Hospital, Ethiopia: a cross-sectional study.

BACKGROUND: Insulin therapy can be inconvenient, painful, burdensome, and restrict patients' daily activities and health related quality of life (HRQOL) due to improper injection techniques or the nature of administration. OBJECTIVE: This study aimed to assess insulin injection practice, HRQOL and predictors among patients treated with insulin at Tikur Anbessa Specialized Hospital (TASH). METHODS: An institutional-based cross-sectional study was conducted among diabetes patients on insulin therapy from May to June 2022. A structured questionnaire was used to collect patient characteristics and insulin injection practice. The validated Amharic version of an EQ-5D-5L tool was used to assess the HRQOL. The data was analyzed using SPSS version 26. The patient data were summarized using descriptive statistics. One-way ANOVA using Kruskal-Wallis H tests was used to assess factors that predict insulin handling practice scores. Multivariate linear regression analysis was used to assess factors affecting HRQOL among diabetes patients treated with insulin. The EQ5D-5L utility scores of the patients were calculated using disutility coefficients taken from the Ethiopian general population. Statistical significance was declared at p-value < 0.05. RESULTS: Of 319 patients who agreed and completed the survey, 51.1% of them were males. Almost half of the participants (n = 158) were > 50 years of age. Among the study participants, 62.1% were only on intermediate acting insulin. A significantly higher proportion of participants 291(91.2%) in this study were taking insulin two times per day. Most of the participants 234(73.4%) had fair practice with a median insulin handling practice score of 38 out of 56. Patient characteristics such as age, educational status, occupation, disease duration, and type of diabetes were significantly association with insulin injection practice (p < 0.05). The mean ± SD utility score of patients were 0.89 ± 0.19 (ranged from -0.04 to 1). Being female (ß = -5.42, 95%CI:-8.63,-2.21, p = 0.001) and treated for type-I diabetes mellitus (ß = + 9.04, 95%CI: 4.23,13.85, p-value < 0.0001) were significantly associated with HRQOL of patients on insulin therapy. CONCLUSION: The study participants had fair practices in insulin handling, storage, and administration techniques, and it was seen that male and type one diabetes patients have a better quality of life compared to their counterparts.