Insulin Injection Research Articles

Insulin-Induced Copeptin Response in Children and Adolescents to Diagnose Arginine Vasopressin Deficiency

Introduction: The diagnosis of arginine vasopressin deficiency (AVD, formerly central diabetes insipidus) remains a challenge. In recent years, stimulated copeptin has emerged as a promising tool to diagnose AVD. Methods: In this single centre retrospective study, we identified paediatric patients with suspected pituitary insufficiency who underwent standard insulin tolerance testing (ITT) previously. Patients with AVD and non-matched controls without polyuria-polydipsia syndrome were identified. Diagnosis of AVD was confirmed retrospectively using comprehensive clinical and diagnostic characteristics. Serum copeptin concentrations were measured using a commercially available automated immunofluorescence assay (B.R.A.H.M.S Copeptin-proAVP KRYPTOR®) in −20°C stored samples collected before and 30, 45, and 60 min after insulin injection. Cut-off analyses were performed using ROC curves. Results: Twenty-five patients with AVD and 43 non-matched controls were available for analysis. Median basal copeptin concentrations of 1.51 pmol/L (IQR: 0.91–1.95; serum osmolarity: 288.5 mmol/L, IQR: 282.3–293.5) increased at a median of 30 min to a maximum of 1.95 pmol/L (IQR: 1.31–2.39) in AVD patients (p = 0.113) and from 4.41 pmol/L (IQR: 3.36–6.68; serum osmolarity: 281.0 mmol/L, IQR: 274.0–286.0, p < 0.001) to a maximum of 8.39 pmol/L (IQR: 4.95–19.72, p < 0.001) in controls. ROC analysis resulted in a cut-off of 3.0 pmol/L for maximum copeptin (91.7% sensitivity, 94.1% specificity) for the diagnosis of AVD. Conclusion: Our results suggest that insulin-stimulated serum copeptin concentrations are a sensitive and specific diagnostic tool for AVD in paediatric patients, which allows us to test multiple pituitary hormone axes simultaneously in a single test.

‘The national health insurance policy provides little to no benefit to young persons living with type 1 diabetes (T1D)’: a qualitative study of T1D management cost-burden in Southern Ghana

BackgroundType 1 diabetes (T1D) management exerts a considerable financial burden on patients, caregivers, and developing nations at large. In Ghana, a key governments effort to attenuate the financial burden of T1D on patients was to fashion safety-net mechanisms through financial risk pooling/sharing known as the National Health Insurance Scheme (NHIS). However, there is limited research on patients and caregivers’ experiences with the cost of managing T1D within the NHIS in Ghana.ObjectiveThis study explored the cost of T1D management, and the impact of the NHIS policy on mitigating costs of care.MethodsA semi-structured interview guide was developed to collect qualitative data from 28 young people living with T1D (PLWD), 12 caregivers, 6 healthcare providers, and other stakeholders in Western, Central and the Greater Accra regions. Multiple data collection techniques including mystery client and in-depth interviews were used to collect data. Thematic content analysis was performed with QSR NVivo 14.ResultsFive key domains/themes which are: cost of T1D management supplies; cost of clinical care; cost of transportation; cost of diet; and NHIS were identified. The daily cost of blood glucose testing and insulin injection per day was between GHC 5–7 (US$ 0.6 to 1.0). The NHIS did not cover supplies such as strips, glucometers, HbA1c tests, and periodic medical tests. Even for those cost which were covered by the NHIS (mainly pre-mixed insulin), marked government delays in funds reimbursement to accredited NHIS facilities compelled providers to push the financial obligation onto patients and caregivers. Such cost obligations were fulfilled through out-of-pocket top-up or full payment of insulin of about GHC 15–25 (US$ 2–4), and GHC 25–50 (US$4–8) depending on the region and place of residence.ConclusionThe cost of managing T1D was a burden for patients and their caregivers. There was a commodification of life-saving insulin on the Ghanaian market, and the NHIS did not function well to ease the cost-burden of T1D management on patients and caregivers. The findings call for the need to scale up NHIS services to include simple supplies, particularly test strips, and always ensure the availability of life-saving insulin in healthcare facilities.

The Efficacy of Video-Assisted Instruction in Preventing Lipohypertrophy in Patients Diagnosed with Type 2 Diabetes

A thick fatty tissue called lipohypertrophy develops in the insulin site as a result of repeated injections at the same location. Patients with diabetes mellitus who use regular insulin are more likely to experience it. The absorption of insulin is impacted in these adipose-rich regions. The purpose of this study was to evaluate how well individuals with diabetes mellitus responded to video- assisted instruction on lipohypertrophy prevention. The aim of the study was to evaluate the efficacy of video- assisted instruction in preventing lipohypertrophy and investigate the relationship between lipohypertrophy preventive pretest knowledge and certain socio- demographic factors. Thirty patients with diabetes mellitus receiving insulin injections made up the total sample size. To choose the samples, a convenient sampling procedure was applied. Using a self-administered questionnaire, the investigators evaluated the participants' degree of knowledge regarding lipohypertrophy prevention during the pretest. A half-hour of video- assisted instruction on lipohypertrophy prevention was conducted on the same day. A posttest using the same instrument was carried out five days later. 10.4% of the samples had strong knowledge during the pretest, 43% had average knowledge, and 46.6% had poor knowledge. Following video-assisted instruction, 71.2% of samples possessed excellent knowledge, 25.5% had average knowledge, and 3.3% had inadequate knowledge regarding lipohypertrophy avoidance. A paired "t"test was employed, and the results indicated a statistically significant increase in knowledge ('t'=9.25, p &lt;0.05). Pretest knowledge scores and a few chosen demographic factors do not correlate. The study came to the conclusion that patients with diabetes mellitus can effectively prevent lipohypertrophy by learning more through video assisted education.

Insulin injection rotation and Diabetes Mellitus nutritional management education

The management of Diabetes Mellitus (DM) involves implementing a healthy lifestyle and pharmacological interventions through the administration of anti-hyperglycemia drugs. An essential aspect of treating DM patients is insulin administration, which facilitates glucose transportation into cells. This study evaluated the effectiveness of insulin injection rotation and nutritional management education for DM.The literature search utilized the keywords "education,"AND "insulin injection," AND "nutritional management," AND "DM", ranged 2021-2023 Searches were conducted on various databases, including Proquest, NCBI, BMC, ScienceDirect, and other relevant platforms such as Google Scholar.Ten journal articles pertinent to the subject matter were identified in the study. Findings indicate that nutritional education facilitates overall health improvement in individuals with DM, contributing to maintaining average body weight and near-normal blood glucose levels. It also enhances lipid profile and insulin receptor sensitivity while being a preventive measure against acute or chronic complications such as hyperglycemia. It is noted that selecting the appropriate injection site can significantly impact patients' blood glucose levels. While it is recommended to administer injections at consistent locations, repetitive use of the same site may pose risks of side effects, such as lipodystrophy.After conducting a comprehensive review of ten journal articles, it has been concluded that insulin injection rotation and nutritional management education are effective for managing DM.

Clinical significance of coefficient of variation in continuous glucose monitoring for glycemic management in children and adolescents with type 1 diabetes.

Coefficient of variation (CV) is an indicator for glucose variability in continuous glucose monitoring (CGM), and the target threshold of %CV in type 1 diabetes is proposed to be ≤36%. This study aimed to evaluate the clinical significance of CV in children and adolescents with type 1 diabetes. Participants included 66 children with type 1 diabetes. A total of 48 participants were treated with multiple daily injections of insulin, and 18 with continues subcutaneous insulin infusion, using intermittently scanned CGM. The frequencies of the CGM metrics and glycosylated hemoglobin values were examined, and the significance of a threshold %CV of 36% was evaluated. The mean frequencies in time in range (TIR), time below range, %CV and the mean glycosylated hemoglobin value were 59.3 ± 16.1, 4.0 ± 3.5, 39.3 ± 6.2 and 7.3 ± 0.8%, respectively. The frequencies of participants who achieved a TIR >70% and a %CV of ≤36% were 24.1 and 27.3%, respectively. A total of 18 participants with a %CV of ≤36% had significantly higher TIR, lower time below range and lower glycosylated hemoglobin than the 48 with a %CV of >36% (72.6 ± 12.6 vs 52.4 ± 13.6, 2.4 ± 1.9 vs 4.6 ± 3.6, 6.9 ± 0.8 vs 7.4 ± 0.7%, respectively). Children and adolescents with type 1 diabetes using intermittently scanned CGM had difficulties in achieving the recommended targets of TIR and CV. However, the target %CV of ≤36% seems to be an appropriate indicator for assessing glycemic control and risk of hypoglycemia in pediatric patients with type 1 diabetes with any treatment.

Self-Care Activities Among Diabetic Patients in an Urban Health Centre in Thirumazhisai, Tamil Nadu: A Cross-Sectional Study.

Background Diabetes is a long-term medical condition characterized by consistently high blood glucose levels, which can be attributed to both genetic and environmental factors. Global diabetes prevalence is predicted to reach 10.4% by 2040, impacting over 642 million people. Diabetes is becoming more common in India; by 2030, an estimated 87 million individuals are predicted to have the disease. Self-care activities are essential for managing diabetes, yet adherence to these practices is often low in developing countries like India due to socioeconomic, cultural, and healthcare barriers. Objective In this study, the self-care practices of diabetic patients who visited an Urban Health Center in Thirumazhisai, Tamil Nadu, were assessed, along with the factors influencing these practices. Methods A three-month cross-sectional study was conducted in a facility with 200 type 2 diabetic patients who had been unwell, for a minimum of a year. The participants were selected via purposeful sampling, and interviews were conducted using the most recent version of the Summary Diabetes Self-Care Activities (SDSCA) questionnaire. The data was analyzed using SPSS version 26 (IBM Corp., Armonk, NY, USA) to discover connections between the duration of diabetes and self-care practices using descriptive statistics and chi-square tests. Results The study found that 136 (68%) of participants tested their blood sugar levels at least once in the preceding three months, 104 (52%) exercised for at least 30 minutes each day, and 96 (48%) of individuals maintained a balanced diet. On the other hand, adherence to insulin injections and oral hypoglycemic medications was lower, at 98 (49%) and 79 (39.5%), respectively. Foot hygiene was also not at its best; only 85 (42.5%) people washed their feet daily. Considerable correlations have been shown between the length of diabetes and particular self-care behaviors, including eating patterns, exercise routines, and foot hygiene. Conclusion The results emphasize the necessity of focused interventions, especially in developing nations, to enhance diabetic patients' self-care behaviors.Tailored, patient-centered strategies are essential to address the complex factors influencing diabetes management, ultimately improving glycemic control and patient outcomes.

FORGETDIABETES proposes radically new approach to diabetes treatment

Type-1 diabetes is a chronic, incurable condition which still requires careful management and regular injections of insulin. Researchers in the FORGETDIABETES project are working to develop a fully implantable bionic invisible pancreas, which will relieve the burden associated with managing type-1 diabetes, as Professor Claudio Cobelli explains.

Educational Interventions for Individuals with Insulin-Treated Type 2 Diabetes Mellitus: A Systematic Review.

To evaluate and synthesize evidence on the impact of educational interventions for individuals with insulin-treated type 2 diabetes mellitus (T2DM). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, five electronic databases (Scopus, PubMed, Medline, CINAHL Plus with Full Text, and Web of Science) were systematically searched in February 2024. The search focused on studies published between 2019 and 2024 that investigated the impact of educational interventions on individuals with insulin-treated T2DM. Reference lists of the included studies were also manually searched. Titles and abstracts were screened for eligibility, and relevant full texts were assessed. Out of 1,032 identified records, 11 studies met the inclusion criteria. According to the data synthesized using a convergent integrated analysis framework, five major themes have emerged: 1) Glycemic control (including subthemes improving HbA1C, decreasing postprandial plasma glucose, and decreasing fasting plasma glucose), 2) Insulin-related complications (including subthemes reducing hypoglycemic events and reducing the size of lipohypertrophy), 3) Knowledge, Attitude, and Practice (including subthemes engaging in self-management, improving insulin injection technique, improving knowledge, and improving attitude toward insulin treatment), 4) Optimal dose of insulin, and 5) Improving quality of life. Educational interventions are crucial for improving diabetes-related outcomes and reducing complications in individuals with insulin-treated T2DM. These interventions enhance knowledge, attitudes, and self-management practices, leading to better glycemic control and quality of life. Healthcare settings should develop and provide tailored educational programs for individuals with insulin-treated T2DM to optimize outcomes and minimize complications.

Prevalence and Impact of Psychological Disorders on Pharmacotherapy of Diabetic Patients in Low Resource Settings: A Prospective Assessment in Primary Healthcare Settings.

Prevalence of psychological disorders among individuals with diabetes is significantly higher as compared to the general population. This study aimed to assess the prevalence and impact of psychological disorders on pharmacotherapy of diabetes patients. This cross-sectional study was conducted at two primary care hospitals in Pakistan from April to June 2023. The nine-item Patient Health Care Questionnaire (PHQ-9) scale was used to assess depression in the study's population, and its effects on pharmacotherapy of diabetes. Chi-square test was used to evaluate relationship between ordinal variables/categorical variables and depression whereas; Student's t-test was used to assess the relationship between numerical variables with depression. A total of 320 patients were assessed, comprising 120 (37.5%) males and 200 (62.5%) females, with a mean age of 52.5 (SD±11.8) years. The average duration of diabetes is 7.0 (SD±5.4). The average PHQ-9 score was 8.3 (SD±5.5). Depression was found to be prevalent in 43.7% of the study population. Gender (female) (p-value 0.002), advanced age (p-value 0.002), lower income (p-value 0.001), education levels (p-value 0.001), longer duration of diabetes (p-value 0.001), poor diabetes control according to BSR value (p-value 0.001), usage of injectable insulin (p-value 0.005), and concomitant diseases (p-value 0.001) were found to be independently linked with depression. Significant association was observed between depression and treatment adherence (p-value 0.0025), number of missed doses (p-value 0.045), and difficulty in diabetes management (p-value 0.0015). Our study highlights significant prevalence of depression in study population and the prevalent depression negatively impacts on treatment adherence. It also revealed that depression complicates diabetes management resulting in poor medication adherence, poor diabetes control and diabetes related complications, making diabetes control more challenging and difficult.

Evaluation of Prothrombin and Activated Partial Thromboplastin Time in Patients with Diabetes Mellitus

Diabetes mellitus (DM) is a metabolic disease accompanied by high blood glucose due to a defect in insulin secretion, insulin activity, or both. High blood glucose levels may lead to serious damage to some organs of the body, mainly blood vessels and nerves. Therefore, this study was conducted to evaluate prothrombin time (PT) and activated partial thromboplastin time (APTT) in diabetic patients. 100 venous blood samples were collected from diabetic patients attending the diabetes clinic in Sebha. Of them, 57 were males and 53 were females, and their ages ranged between 15-88 years. out of 100, 48 Were treated with insulin-regulating tablets and 52 Were treated with insulin injections. 34 blood samples were collected from healthy people (15 females and 19 males). They were used as a control group, aged between 14-55 years. 4 ml of venous blood was drawn, and 2 ml was placed in containers containing the anticoagulant sodium citrate to perform the PT and APTT. Place 2 ml of sample in tubes containing sodium fluoride anticoagulant to perform a fasting blood sugar (FBS). Place the tubes in a centrifuge at 3000 rpm to obtain plasma. The results showed the mean of PT in patients was (19.4 ± 3.6), the mean APTT was (35.9 ± 1.5) and the Mean FBS was (229.7 ± 80.39), whereas the mean PT, APTT, and FBS in control were (12.8 ± 1.6), (25.4 ± 2.1), and (91.9 ± 12.5) respectively. there was a significant increase of PT and APTT in patients compared to control (P&lt;0.05), PT and FBS were higher in patients who used insulin injection with significant differences(P&lt;0.05), while no significant differences were in APTT (P &gt; 0.05). The present study observed a statistically significant increase in PT and APTT among patients compared to controls, it would be helpful to incorporate coagulation screening as a routine investigation for the better management of diabetic patients.

Prevalence and associated factors of lipodystrophy in type 1 diabetic children and adolescents at Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia

IntroductionLipodystrophy can cause poor glycemic control in addition to cosmetic problems in children and adolescents with type 1 diabetes mellitus. However, data on its prevalence and associated factors is scarce among children and adolescents who live in developing countries like Ethiopia.ObjectiveTo determine the prevalence and identify associated factors of lipodystrophy in children and adolescents with type 1 diabetes mellitus who visited the endocrinology clinic of Ayder Comprehensive Specialized Hospital between May 1 and July 31, 2020.MethodThis was an institution-based cross-sectional study conducted on 57 children and 65 adolescents with type 1 diabetes mellitus who had been taking insulin injections for a year or more. The dependent variable was lipodystrophy. A pretested, structured questionnaire was used to collect data related to lipodystrophy and other characteristics. The principal investigator oversaw the data collection, which was done by pediatric and child health specialty residents with training. Data was subjected to descriptive statistics, and predictors of lipodystrophy were identified by fitting a multivariable logistic regression model. Statistical significance was declared at p < 0.05.ResultsMore than half (53.3%) of patients were in the age range of 13 to 17. The male-to-female ratio was almost 1:1. Educational status for 63.1% of patients was primary school. Four-fifths of patients were residing in urban areas. Of the 122 participants, 60 (49.2%) had lipodystrophy (48.3% lipohypertrophy and 0.8% lipoatrophy), with grade II lipohypertrophy being the most common type at 81.7%. The thigh was the most common site of lipodystrophy. In multivariable regression analysis, the long duration of insulin injection (AOR = 3.6, 95% CI, 1.5 to 9.0, p = 0.005) and inappropriate rotation of the injection site (AOR = 9.0, 95% CI, 2.2 to 37.0, p = 0.002) were significantly associated with lipodystrophy. HbA1c testing was conducted for 70 patients, and poor glycemic control (HbA1c ≥ 7%) was found in 43 (61.4%) of them. Patients with lipodystrophy were more likely to have poor glycemic control (75%) than those without lipodystrophy (47.1%) (p = 0.016).ConclusionThe prevalence of lipodystrophy was comparable with other studies. Long duration of insulin injection and improper rotation of the injection site are associated with an increased risk of lipodystrophy. Patients with lipodystrophy were more likely to have poor glycemic control, defined by higher HgA1c, than those without lipodystrophy. Proper education of patients and their parents must include correct injection techniques, rotating injection sites, and changing injection sites intermittently to lessen the risk of developing lipodystrophy.

Impact of triple transmembrane regulator therapy on glucose metabolism in cystic fibrosis related diabetes during clinical practice

AimsTo evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on Cystic Fibrosis Related Diabetes (CFRD) glycemic control and insulin treatment in patients with CFRD during clinical practice. MethodsWe carried out a retrospective observational study of 23 adult patients with CFRD who started treatment with ETI. They had, at least, one F508del mutation. Data were collected before ETI initiation and 3, 6, and 12 months after. ResultsGlycemic control measured by HbA1c significantly improved by 0.3 % (0.1–0.5) after 3 months of ETI therapy (p = 0.004) and kept this improvement during follow-up (p < 0.001). The proportion of patients needing multiple daily injections of insulin was reduced by 16 % (p = 0.023). Total daily insulin dose dropped by 0.12 (0.05–0.18) UI/kg/day (p < 0.001). Data derived from Flash Continuous Glucose Monitoring (CGM) for patients treated with insulin stayed unchanged after insulin reduction, except for a significant 8 % (0.3–15.6) increase in the Time In Tight Range (TITR) between 70 and 140 mg/dL (p = 0.043). ConclusionETI therapy impacted CFRD in clinical practice reducing insulin needs and improving glycemic control measured by HbA1c and CGM. The improvements can be observed from the first 3 months of treatment.

Authentication of the shelf-life of NPH injectable insulins samples using NIR and MS spectral fingerprints

Insulin is essential for regulating glucose levels, and its hormonal deficiency leads to diabetes. Treatment involves the use of different types of insulin tailored to individual needs. Properly stored and transported Neutral Protamine Hagedorn (NPH) insulin remains effective and stable, highlighting the importance of quality control to ensure its efficacy and patient safety. This study aims to develop an analytical method to evaluate the shelf-life of NPH injectable insulin samples while preserving packaging integrity. The approach consisted of analyzing intact insulin samples, with and without expired shelf-life dates, using near-infrared spectroscopy (NIR) obtained from two instruments: a benchtop and a portable device. These measurements were coupled with chemometric methods, specifically single-class classification algorithms. The classifiers considered were Data Driven-Soft Independent Modeling of Class Analogy (DD-SIMCA) and One-Class Partial Least Squares (OC-PLS). For benchtop NIR, the DD-SIMCA method, with Savitzky-Golay smoothing preprocessing (41-point window) and baseline offset (BO), achieved excellent results, reaching 100% sensitivity, specificity, and efficiency in both training and test sets. As for portable NIR, the most effective methods were DD-SIMCA and OC-PLS, using datasets preprocessed with Savitzky-Golay smoothing with first derivative, second-order polynomial (SGD-1st-2nd), and 9-point windows combined with Standard Normal Variate (SNV), and Savitzky-Golay smoothing filters (SGS) using second-order polynomial and 7-point windows combined with baseline offset (BO) and Multiplicative Scattering Correction (MSC). The results were corroborated by mass spectrometry, correlating the structural changes of degraded insulin with NIR data. The proposed methodology is a promising tool for non-destructive, rapid, and cost-effective authentication of the preservation state of NPH insulin, aligning with green chemistry principles and allowing for in-situ evaluation, thereby preserving medication integrity.

Self-management interventions for gestational diabetes in Africa: a scoping review

BackgroundGestational diabetes (GD) can threaten the health of both the mother and the foetus if it is not effectively managed. While there exists a growing body of research on self-management interventions for GD, there is a lack of reviewed studies regarding the various self-management interventions in Africa. The purpose of this review is to map the evidence of self-management interventions for GD in Africa.MethodsSearches for records were conducted in four major databases, including PubMed, PubMed Central, Science Direct and Journal Storage. Additional documents from Google and Google Scholar were also added. The guidelines for conducting scoping reviews by Arksey and O’Malley were followed.ResultsThe results revealed that intermittent fasting, education on diet, insulin injection, blood glucose monitoring, physical activities, lifestyle modification and foot care were the available self-management interventions for GD in Africa. Most of the reviewed studies reported intermittent fasting and patient education as effective self-management interventions for GD in Africa. The barriers identified in the reviewed studies were either patient-related or facility-related. Patient-related barriers included lack of awareness, and negative attitude, while facility-related barriers included lack of access to education on GD, especially, face-to-face educational interventions.ConclusionIt is crucial to consider the cultural and personal needs, as well as the educational level of women with gestational diabetes when creating an effective self-management intervention. Optimal results can be achieved for self-management of gestational diabetes by integrating multidisciplinary approaches.

Intracerebroventricular insulin injection acutely normalizes the augmented exercise pressor reflex in male rats with type 2 diabetes mellitus.

The exercise pressor reflex (EPR) is exaggerated in type 2 diabetes mellitus (T2DM), but the underlying central nervous system aberrations have not been fully delineated. Stimulation of muscle afferents within working skeletal muscle activates the EPR, by sending information to neurons in the brainstem, where it is integrated and results in reflexively increased mean arterial pressure (MAP) and sympathetic nerve activity. Brain insulin is known to regulate neural activity within the brainstem. We hypothesize that brain insulin injection in T2DM rats attenuates the augmented EPR, and that T2DM is associated with decreased brain insulin. Using male Sprague-Dawley rats, T2DM and control rats were generated via an induction protocol with two low doses of streptozotocin (35 and 25mg/kg, i.p.) in combination with a 14-23-week high-fat diet or saline injections and a low-fat diet, respectively. After decerebration, MAP and renal sympathetic nerve activity (RSNA) were evaluated during EPR stimulation, evoked by electrically induced muscle contraction via ventral root stimulation, before and after (1 and 2h post) intracerebroventricular (i.c.v.) insulin microinjections (500mU, 50nl). i.c.v. insulin decreased peak MAP (ΔMAP Pre (36±14mmHg) vs. 1h (21±14mmHg) vs. 2h (11±6mmHg), P<0.05) and RSNA (ΔRSNA Pre (107.5±40%), vs. 1h (75.4±46%) vs. 2h (51±35%), P<0.05) responses in T2DM, but not controls. In T2DM rats, cerebrospinal fluid insulin was decreased (0.41±0.19 vs. 0.11±0.05ng/ml, control (n=14) vs. T2DM (n=4), P<0.01). The results demonstrated that insulin injections into the brain normalized the augmented EPR in brain hypoinsulinaemic T2DM rats, indicating that the EPR can be regulated by brain insulin. KEY POINTS: The reflexive increase in blood pressure and sympathetic nerve activity mediated by the autonomic nervous system during muscle contractions is also known as the exercise pressor reflex. The exercise pressor reflex is dangerously augmented in type 2 diabetes, in both rats and humans. In type 2 diabetic rats both cerebrospinal fluid insulin and phosphoinositide 3-kinase signalling within cardiovascular brainstem neurons decrease in parallel. Brain insulin injections decrease the magnitude of the reflexive pressor and sympathetic responses to hindlimb muscle contraction in type 2 diabetic rats. Partial correction of low insulin within the central nervous system in type 2 diabetes may treat aberrant exercise pressor reflex function.

Generation of Insulin-Producing Cells from Canine Bone Marrow-Derived Mesenchymal Stem Cells: A Preliminary Study.

Cell-based therapy using insulin-producing cells (IPCs) is anticipated as an alternative treatment option to insulin injection or pancreatic islet transplantation for the treatment of diabetes mellitus in both human and veterinary medicine. Several protocols were reported for the differentiation of mesenchymal stem cells (MSCs) into IPCs; to date, glucose-responsive IPCs have only been obtained from canine adipose tissue-derived MSCs (cAD-MSCs), but not from canine bone marrow-derived MSCs (cBM-MSCs). Therefore, this study aims to generate in vitro glucose-responsive IPCs from cBM-MSCs using two differentiation protocols: a two-step protocol using trichostatin (TSA) and a three-step protocol using mercaptoethanol to induce pancreatic and duodenal homeobox gene 1 (PDX-1) expression. A single experiment was carried out for each protocol. BM-MSCs from one dog were successfully cultured and expanded. Cells exposed to the two-step protocol appeared rarely grouped to form small clusters; gene expression analysis showed a slight increase in PDX-1 and insulin expression, but no insulin protein production nor secretion in the culture medium was detected either under basal conditions or following glucose stimulation. Conversely, cells exposed to the three-step protocol under a 3D culture system formed colony-like structures; insulin gene expression was upregulated compared to undifferentiated control and IPCs colonies secreted insulin in the culture medium, although insulin secretion was not enhanced by high-glucose culture conditions. The single experiment results suggest that the three-step differentiation protocol could generate IPCs from cBM-MSCs; however, further experiments are needed to confirm these data. The ability of IPCs from cBM- MSCs to produce insulin, described here for the first time, is a preliminary interesting result. Nevertheless, the IPCs' unresponsiveness to glucose, if confirmed, would affect its clinical application. Further studies are necessary to establish a differentiation protocol in this perspective.

Intestinal glucagon-like peptide-1: A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic mice.

Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions. However, the patho-genesis of hypoglycaemic counterregulation is still unclear. Glucagon-like peptide-1 (GLP-1) and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus (T1DM). The role of GLP-1 in counterregulatory dys-function during hypoglycaemia in patients with T1DM has not been reported. To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice. T1DM was induced in C57BL/6J mice using streptozotocin, followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia (DH5). Immunofluorescence, Western blot, and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon (GCG) secretion. The GLP-1 receptor agonist GLP-1(7-36) or the antagonist exendin (9-39) were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice. The expression levels of intestinal GLP-1 and its receptor (GLP-1R) were significantly increased in DH5 mice. Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex, leading to dysfunction of adrenal counterregulation during hypoglycaemia. DH5 mice showed increased pancreatic δ-cell mass, cAMP levels in δ cells, and plasma somatostatin concentrations, while cAMP levels in pancreatic α cells and plasma GCG levels decreased. Furthermore, GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group. Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway. Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia, leading to reduced appetite and compromised secretion of adrenaline, noradrenaline, and GCG during hypo-glycaemia.

Health beyond biology: the extended health hypothesis and technology.

There are ethical dilemmas faced by clinicians when responding to using unregistered medical devices, such as innovative internet technologies for managing type 1 diabetes mellitus. This chronic disease significantly impacts patients' health, requiring intensive daily activities like blood glucose monitoring, insulin injections, and specific dietary recommendations. Recent technological advances, including continuous glucose monitors and insulin pumps, have been shown to improve glycemic control. Di-it Yourself Artificial Pancreas Systems are emerging open-source automated delivery methods initiated by the diabetes community, although they are not clinically evaluated and present a liability challenge for healthcare providers. To use them or not? Should parents and healthcare providers use such technology that helps, but is not proven?Having all of that in mind, we argue that the World Health Organization's (WHO) definition of health is outdated, advocating for the "Extended Health Hypothesis". This hypothesis claims that health extends beyond traditional biological boundaries to include essential functional structures like diabetes-related technology, making technology a part of a patient's health. This view aligns with the "Extended Mind Hypothesis," suggesting that health should include elements beyond organic material if they are vital to a patient's functions.In the commentary, we highlight that both naturalist and normative conceptions of health support the extended health hypothesis, emphasizing that human health is not confined to organic material. This perspective raises critical questions about whether devices like insulin pumps and continuous glucose monitors are integral to a patient's health and whether their malfunction constitutes a form of disease. Devices are considered integral to health, there is no ethical dilemma in using unregistered medical devices for managing type 1 diabetes. Finally, we call for reevaluating the definitions of health and patients, particularly for children with type 1 diabetes using advanced technologies. It asserts that the optimal use of such devices represents a new form of health, creating a health-device symbiosis that should be evaluated with the child's best interests in mind.

Islet transplantation in Korea.

Type 1 diabetes mellitus is characterized by absolute insulin deficiency, which requires life-long insulin replacement. Exogenous multiple-daily insulin injections are most commonly prescribed for patients with type 1 diabetes mellitus. However, exogenous insulin supply often fails to cope with real-time changing life-log variables, such as activity, diet and stress, which results in recurrent hypo- and hyperglycemia in patients with type 1 diabetes mellitus. Islet transplantation is an ideal method to treat patients with type 1 diabetes mellitus, as it can restore the endogenous capacity of glucose-stimulated insulin secretion. However, due to donor scarcity and technical barriers, only a limited number of islet transplantations have been carried out in Asia, including South Korea. Since 2013, our center has carried out two allogenic islet transplantations, with one case leading to near total insulin independence after one-to-one islet transplantation. Although the other patient failed to restore endogenous insulin production, there was a remarkable improvement in hypoglycemia. We speculate that islet transplantation remains an important and ideal treatment option for patients with type 1 diabetes mellitus who suffer from recurrent severe hypoglycemia.

Flash Glucose Monitoring is Associated with HbA1c Improvement in Type 2 Diabetes Managed with Multiple Daily Injections of Insulin in the UK: A Retrospective Observational Study.

There is a growing body of evidence demonstrating the benefit of flash glucose monitoring in people living with type 2 diabetes mellitus (T2DM). This real-world study aimed to evaluate the effect of initiating flash glucose monitoring on change in HbA1c after 3-6months in adults living with T2DM treated with multiple daily injections of insulin. A retrospective observational study using data from ten clinical centres in the UK for adults with T2DM treated with multiple daily injections of insulin for at least 1year was conducted. Patients who had been using the FreeStyle Libre/Libre 2 Flash Glucose Monitoring System for at least 3months with baseline HbA1c 64-108mmol/mol (8.0-12.0%) recorded up to 3months prior to system use were included. Pregnant patients and those on dialysis were excluded. Patients with an HbA1c value measured 3-6months after commencing flash glucose monitoring were included in the final analysis for evaluation of change. In total, 87 patients were included in the final analysis (mean age, 60.0 ± 11.8years, 60.9% male, mean body mass index (BMI), 31.6 ± 5.4 [mean ± SD]). From a mean baseline HbA1c of 80 ± 11mmol/mol (9.5% ± 1.0%), HbA1c lowered by 11 ± 14mmol/mol (1.0% ± 1.3%) at 3-6months (p < 0.0001). A decrease was observed independent of age, baseline HbA1c, sex, duration of insulin use and BMI subgroups. Initiation of flash glucose monitoring was associated with a clinically and statistically significant improvement in HbA1c in a real-world setting at 3-6months.