Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

Insulin is present in nasal mucus and plays an important role in the survival and activity of individual olfactory sensory neurons (OSNs) via insulin receptor-mediated signaling. However, it is unclear whether insulin acts prophylactically against olfactotoxic drug-induced olfactory epithelium (OE) injury, and whether the degree of damage is affected by the concentration of insulin in the nasal mucus. The apoptosis-inducing drug methimazole was administered to the nasal mucus of diabetic and normal mice along with different concentrations of insulin. Immunohistochemical analysis was used to assess the relationship between damage to the OE and the mucus insulin concentration and the protective effect of insulin administration against eosinophilic cationic protein (ECP)-induced OE injury. Diabetic mice had lower concentrations of insulin in their nasal mucus than normal mice (diabetic vs. normal mice, p < 0.001). Methimazole administration reduced the number of OSNs in normal mice and had a more marked effect in diabetic mice. However, unilateral insulin administration prevented the methimazole-induced reduction in the number of OSNs on the ipsilateral side but not on the contralateral side (OSNs; Insulin vs. contralateral side, p < 0.001). Furthermore, intranasal ECP administration damaged the OE by inducing apoptosis (OSNs; ECP vs. contralateral side, p < 0.001), but this damage was largely prevented by insulin administration (OSNs; Insulin + ECP vs. contralateral side, p = 0.36), which maintained the number of mature OSNs. The severity of methimazole-induced damage to the OE is related to the insulin concentration in the nasal mucus (Correlation between the insulin concentration in nasal mucus and the numbers of OSNs, R2 = 0.91, p < 0.001), which may imply that nasal insulin protects OSNs and that insulin administration might lead to the development of new therapeutic agents for ECP-induced OE injury.

Reliability of Inpatient CGM: Comparison to Standard of Care

Background: Optimal inpatient glycemic management targets a blood glucose (BG) of 140-180 mg/dL and is an important safety measure for hospitalized patients with hyperglycemia. Traditional barriers to appropriate insulin administration include incorrect timing of prandial insulin administration, failure to administer basal insulin to persons with insulin deficiency/type 1 diabetes mellitus (DM), and inaccurate insulin dosing or timing resulting in hypoglycemia. Given the ongoing rapid assimilation of technology to manage our patients with DM, we investigated the use of continuous glucose monitoring (CGM) in the inpatient setting as a potential solution to traditional barriers to optimal hyperglycemia management for inpatient care. In this study, we evaluated the efficacy of use of inpatient CGM for insulin dosing in comparison with current standard of care and whether CGM could aid in minimizing hypoglycemic events. Methods: This study evaluated the use of Abbott professional (blinded) Freestyle Libre CGMs in participants treated with basal bolus insulin administered with subcutaneous insulin (basal bolus therapy [BBT]: n = 20) or on intravenous insulin (IVI) infusions (n =16) compared with standard point of care (POC) BG measurements. All participants on IVI were admitted with a diagnosis of diabetic ketoacidosis (DKA). The CGM data was not available in real time. Sensors were removed at the time of discharge and data uploaded to Libre View. Continuous BG data were aggregated for each subject and matched to POC BG or lab chemistry values within five minutes. The POC BG results were assessed for comparability (CGM vs standard BG testing). Data were further analyzed for clinical decision-making for correction insulin. Results: The overall mean absolute relative difference including both IVI and BBT groups was 22.3% (SD, 9.0), with a median of 20.0%. By group, the IVI arm mean was 19.6% (SD, 9.4), with a median of 16.0%; for BBT, the arm mean was 24.6% (SD, 8.1), with a median 23.4%. Using the Wilcoxon two-sample test, the means were not different ( P = .10), whereas the medians were ( P = .015). The CGM consistently reported lower glucose values than POC BG in the majority of paired values (BBT arm mean difference = 44.8 mg/dL, IVI mean difference = 19.7 mg/dL). Glucose results were in agreement for the group 83% of the time with Bland-Altman Plot of Difference versus the mean of all glucometric data. Analysis of correction dose insulin using either CGM or POC BG values resulted in a negligible difference in calculated insulin dose recommended in those receiving subcutaneous insulin. Corrective doses were based on weight and insulin sensitivity (type 1 vs type 2 DM). Participants initially on IVI were included in a data set of BBT once IVI therapy ceased and basal bolus insulin regimen was started. The data of all basal bolus therapy participants with 1142 paired values of CGM versus POC glucose were used. The dosing difference was less for CGM than POC BG in the majority of paired values, and there was an absolute difference in dose of insulin of only 1.34 units. In the IVI group with 300 paired values of CGM versus POC glucose, there was an absolute difference in dose of insulin of only 0.74 units. About a third of the patients studied in the BBT arm experienced a hypoglycemic event with POC BG <70 mg/dL. If used in real time, CGM would have identified a hypoglycemic event for our patients on average 3 hours and 34 minutes before it was detected by standard POC BG. Two participants incurred severe nocturnal hypoglycemia during the study with POC BG <54 mg/dL with hypoglycemia detected on CGM up to 3 hours and 42 minutes before POC testing. Conclusions: These results suggest that the use of inpatient CGM arrives at similar correction insulin dosing. The routine use of CGM for inpatients would consistently underestimate the BG compared with POC BG and could aid in minimizing and predicting hypoglycemia in the hospital setting. Our data support that the model of adoption of real-time inpatient CGM technology is anticipated to have significant impact in the clinical setting in efforts to maintain adequate glycemic control targeting BG 140-180 mg/dL while minimizing the frequency of hypoglycemic events.

Needle Technology for Insulin Administration: A Century of Innovation

Innovations in syringe and pen needle (PN) technology over the last 100 years have led to important advances in insulin delivery for people with diabetes, paralleling the strides made in developing recombinant DNA human insulin and insulin analogs with varying onset and duration of action. In this review, the history of advances in insulin delivery is described, focusing on progress in syringe, needle, and PN technologies. The early glass and metal syringes that required sterilization by boiling have been replaced by disposable, single-use syringes or pens with clear labeling for precise insulin dosing. The early needles ranging in length from 19 to 26 mm that required manual sharpening against a whetstone have been replaced by syringe needles of 6 mm and PNs of 4 mm in length as slender as 34 gauge. Imaging studies using ultrasound and computed tomography measured the thickness of skin and subcutaneous tissue layers to show feasibility of targeted insulin administration with shorter needles. These developments, coupled with innovations in needle/PN wall and tip structure, have led to improved injection experience for people with diabetes. It is also important to acknowledge the role of injection technique education, together with these advances in injection technology, for improving clinical outcomes and patient satisfaction. With continued projected growth of diabetes prevalence, particularly in developing countries where expensive and complex insulin delivery systems may not be practical, insulin syringes and pens will continue to serve as reliable and cost-effective means of insulin delivery for people with diabetes.

Acute Hypoglycemia in Emergency Room: A Review

Hypoglycemia is frequently encountered in the emergency department (ED) and has potential for serious morbidity. The incidence and causes of iatrogenic hypoglycemia are not known. We aim to describe how often the cause of ED hypoglycemia is iatrogenic and to identify its specific causes. Adult patients with a chief complaint or ED diagnosis of hypoglycemia, or an ED glucose value of ≤70 milligrams per deciliter (mg/dL) between 2009–2014. Two independent abstractors each reviewed charts of patients with an initial glucose ≤ 50 mg/dL, or initial glucose ≥ 70 mg/dL with a subsequent glucose ≤ 50 mg/dL, to determine if the hypoglycemia was caused by iatrogenesis. In ED patients with hypoglycemia, iatrogenic causes are relatively common. The most frequent cause was insulin administration for hyperkalemia and uncomplicated hyperglycemia. Additionally, patients at risk of hypoglycemia in the absence of insulin, including those with alcohol intoxication or poor nutritional status, should be monitored closely in the ED.

Suicidality and Self-Harming Behaviors in Patients with Prader-Willi Syndrome (PWS): Case Report and Literature Review

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder which is often associated with significant behavioral challenges and poor intellectual functioning. Research has shown that individuals with PWS are more likely to experience mental health problems, have higher relapse rates, and are at risk of self-harming behavior. Although PWS is associated with mild intellectual disability, which in itself confers a higher mortality rate, suicidality in this population is so far unreported in the literature. We present the case of an 18-year-old male patient who was admitted to our facility following exogenous insulin administration with suicidal intent. The main clinical characteristics, self-harming behaviors, and suicide risk factors of patients with PWS are discussed in this report. The article’s objective is to redirect clinicians’ attention to carefully screen and treat the underlying behavioral problems in PWS patients.

Intravenous insulin administration preparation for myocardial 18F-fluorodeoxyglucose viability imaging has the potential to reduce radiation exposure dose

Purpose This study aimed to identify and validate the optimal 18F-FDG activity and acquisition time for cardiac viability imaging with intravenous insulin administration based on a fixed 18F-FDG activity. Methods Cardiac positron emission tomography (PET) images from 30 patients with coronary artery disease (CAD) were retrospectively reconstructed into 900, 360, 180, 90, and 45 s durations. An optimal product of the maximum standardized uptake value (SUV) of the myocardium and segmental uptake (SU) and acquisition time (MSAT) was determined through a receiver operating characteristic curve. The optimal acquisition time (OAT) was equal to MSAT divided by mean SUV of the myocardium (MyoSUV) and validated in another 26 patients with CAD. Results The MyoSUV, mean SUV of the blood, SU, and their biases on reconstructed image durations of 90, 180, and 360 s were equivalent to those on an image duration of 900 s. The optimal MSAT was 848.2. In the validation group, the OAT was 129 ± 76 s (95% confidence interval, 99–160), approximately one-third of the usual acquisition time. The MyoSUV and SU were equivalent for the difference (0.15 ± 0.21, P < 0.001; −0.01 ± 0.03, P < 0.001) between PET image duration of OAT and 600 s (7.71 ± 3.01 vs. 7.56 ± 2.94, 67.1 ± 15.4% vs. 67.7 ± 15.6%). Conclusion Intravenous insulin administration preparation has the potential to reduce radiation exposure and acquisition time of cardiac 18F-FDG viability imaging without losing the accurate measurement of MyoSUV and SU when reaching an OAT.