Glucagon Injection Research Articles

Difficulties in Correction of Recurrent Hypoglycemia in a Patient With a Progressive Course of Malignant Metastatic Insulinoma

This article describes a clinical observation of a patient with a progressive course of malignant metastatic insulinoma, despite repeated embolization and chemoembolization (CE) of the right and left hepatic arteries with doxorubicin and gemcitabine, with metastatic liver lesion and subsequent increase in the size of secondary foci. The key clinical problem was severe recurrent hypoglycemia, which persisted against the background of massive intravenous (IV) glucose infusions, short-acting somatostatin therapy, and subcutaneous (SC) glucagon injections, which not only was an impediment to the pathogenic cytostatic therapy but also has led to the fatal outcome of the patient. J Endocrinol Metab. 2020;10(5):140-143 doi: https://doi.org/10.14740/jem666

Glucose Sensor Accuracy After Subcutaneous Glucagon Injections Near to Sensor Site.

Background: Integrated hormone delivery and glucose sensing is warranted, but system performance could be challenged by glucose sensor susceptibility to pharmacological interferences. The aim of this study was to compare sensor accuracy (Medtronic Enlite 2®) after subcutaneous (s.c.) administration of low-dose glucagon near to versus remote from sensor site. Methods: Twelve adults with insulin-pump-treated type 1 diabetes wore two continuous glucose monitors (CGMglucagon and CGMcontrol) placed on each side of the abdomen before, during, and after two overnight 14-h in-clinic visits. During each visit, a s.c. 100 μg glucagon injection was administered 2 cm next to the CGMglucagon followed by another injection of 100 μg glucagon 2 h later at the same site. CGM performance was evaluated using 4-h in-clinic Yellow Spring Instrument (YSI) measurements and 3-day self-monitoring of blood glucose (SMBG) in free-living conditions. Results: Using YSI as comparator, no difference in the median absolute relative difference (MARD) for CGMglucagon (15.7%) and CGMcontrol (13.4%) was found (P = 0.195). Similarly, no difference in MARD was found between CGMglucagon (11.0%) and CGMcontrol (6.2%) using SMBG as comparator (P = 0.148). Values in zone A + B of Clarke error grid analysis did not differ between CGMglucagon and CGMcontrol using YSI (93.9% vs. 91.1%, P = 0.250) and SMBG (97.3% vs. 95.0%, P = 0.375) as reference measurement. The precision absolute relative deviation between sensors was 13.7%. Conclusions: Sensor accuracy was not significantly affected by administration of s.c. glucagon near to sensor site.

Usability of Nasal Glucagon Device: Partially Randomized Caregiver and Third-Party User Experience Trial with Simulated Administration at a Japanese Site.

IntroductionGlucagon is the only approved medicine for severe hypoglycemia available for caregivers of people with diabetes. Nasal glucagon (NG) was recently approved in the USA as a needle-free, ready-to-use alternative to injectable glucagon. This simulated user experience study in Japan compared NG and intramuscular glucagon (IMG) administration by caregivers, and NG administration by untrained third parties.MethodsThis was an open-label, single-center, partially randomized crossover, simulated user experience trial conducted in Japan (October 2018 to December 2018). Caregivers who live with and care for a relative with diabetes were randomized (1:1, stratified by patient diabetes type 1 or 2) to one of two simulated administration sequences (group 1: NG then IMG; group 2: IMG then NG). Caregivers received training on each device 2 weeks before simulated administration of the device. Third parties received no training and only conducted simulated NG administration. Outcome measures included the percentage of successful administrations (based on critical step completion and dose; primary outcome), time to complete administration, and user satisfaction/preferences.ResultsIn caregivers (N = 19), the percentage of successful administrations was greater (89.5% vs 26.3%, P < 0.001) and mean time to complete administration was shorter (23.9 vs 207.3 s, P < 0.001) with NG than with IMG. In third parties (N = 20), 95% of NG administration attempts were successful (mean time to complete administration, 55.5 s). All caregivers and 80% of third parties reported that the NG device was easy to use. All caregivers and 70% of third parties were confident and willing to use the device in a real emergency, and more than 80% of caregivers preferred the NG device to IMG.ConclusionThis simulated user experience study confirmed that glucagon administration using a nasal delivery device was quicker, easier, and had a higher success rate than intramuscular administration in Japan, where the glucagon injection kit is not available.FundingEli Lilly.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s13300-019-00711-1) contains supplementary material, which is available to authorized users.

Transcriptional regulation of the AMP-activated protein kinase and glycolipid metabolism-related genes by insulin and glucagon in blunt snout bream (Megalobrama amblycephala): A comparative study

In this study, the effects of insulin and glucagon administration on the glycolipid metabolism of blunt snout bream (Megalobrama amblycephala) were investigated. Fish (average weight 49.5 ± 0.8 g) were intraperitoneally injected with a 0.9% saline solution, a bovine insulin (0.052 mg/kg body weight) and a bovine glucagon (0.075 mg/kg body weight), respectively. Then, samples were taken at 0, 1, 2, 4, 8 and 12 h post injection. The results showed that insulin load induced a significant decrease of plasma glucose level with the minimum observed at 1 h, while the opposite was true after glucagon injection (the highest value was attained at 4 h). After that, plasma glucose levels gradually returned to the normal value. Plasma triglycerides (TG) levels significantly declined during the first 2 h after insulin injection. Then, it increased significantly from 2 to 4 h, and gradually returned to the normal value. The glucagon administration significantly decreased plasma TG levels with the minimum value found at 8 h post-injection. Then, it significantly increased and returned to the basal value with further increasing times. Insulin injection resulted in a significantly increased liver glycogen and lipid contents, which peaked at 2 and 1 h, respectively. However, glucagon injection induced a significant decrease of both parameters. Subsequently, they gradually returned to the normal values. Besides, insulin load significantly decreased the transcriptional levels of AMPKα1, AMPKα2, PEPCK, FBPase, G6pase, PPARα, CPT Ⅰ and ACO during the first 4 h. However, those of GLUT2, GK, PK, SREBP1, FAS and ACCα all increased significantly during the 2–4 h. After the glucagon injection, the transcriptional values of AMPKα1, AMPKα2, PEPCK, FBPase, G6pase, PPARα, CPT I and ACO all increased significantly during the first 8 h, whereas the opposite was true for the remaining indicators during the first 4 h. Overall, exogenous insulin and glucagon significantly affected the glycolipid metabolism of Megalobrama amblycephala. Insulin injection significantly decreased plasma glucose level, but activated AMPK, thus promoting glucose transportation, glycogenesis, glycogenesis and lipogenesis coupled with the depression of gluconeogenesis and fatty acid oxidation, whereas the opposite was true after the glucagon load.

Impact of Intravenous Injection of Glucagon on Anastomotic Leakage in Esophagectomy

Impact of Intravenous Injection of Glucagon on Anastomotic Leakage in Esophagectomy

Preference for Subcutaneously Administered Low-Dose Glucagon Versus Orally Administered Glucose for Treatment of Mild Hypoglycemia: A Prospective Survey Study.

IntroductionIntensive insulin treatment for type 1 diabetes is associated with high risk of mild hypoglycemia. Mild hypoglycemia is usually treated orally with glucose, which may contribute to weight gain. Subcutaneous injection of low-dose glucagon may be a new treatment option for some occasions of mild hypoglycemia in individuals aiming for optimal glycemic control without gaining weight. We investigated under which occasions patients were interested to use low-dose glucagon.MethodsIn a prospective 2-week event-driven survey, participants registered every event of mild hypoglycemia (sensor or blood glucose ≤ 3.9 mmol/l and/or hypoglycemia symptoms). For each hypoglycemia event, participants registered whether they would have preferred to use low-dose glucagon if the treatment had been available.ResultsA total of 51 participants (13 men, mean ± SD age 43.6 ± 12.5 years, HbA1c 7.3 ± 0.7% (57 ± 8 mmol/mol), BMI 24.9 ± 3 kg/m2) were included. Each participant had on average 10 (range 3–23) mild hypoglycemia events during the 2-week survey period. Glucagon was preferred in 58% of the 514 mild hypoglycemia events (p > 0.05). Twelve percent of the participants had no desire to use glucagon for any hypoglycemia event. The preference pattern did not differ between sex, patient treatment modalities, and possible causes for hypoglycemia (all p > 0.05).ConclusionThis study showed that a majority of our participants with type 1 diabetes were interested in using low-dose glucagon for the treatment of mild hypoglycemia.FundingThis work was funded by a research grant from the Copenhagen University Hospital Hvidovre and by the Danish Diabetes Academy supported by the Novo Nordisk Foundation.

Needle-free glucagon formulation aims to simplify emergency treatment of severe hypoglycemia

In July, FDA approved glucagon nasal powder (Baqsimi—Eli Lilly), the first glucagon therapy that can be administered without an injection for emergency treatment of severe hypoglycemia in patients with diabetes ages 4 years and older. The agent comes in a single-use dispenser containing one dose of glucagon 3 mg, which is administered into one nostril. Because inhalation is not required, the drug can be successfully administered by another person if the receiver is unconscious. “[U]ntil now, people suffering from a severe hypoglycemic episode had to be treated with a glucagon injection that first had to be mixed in a several-step process,” noted Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research. “This new way to administer glucagon may simplify the process, which can be critical during an episode [of severe hypoglycemia], especially since the patient may have lost consciousness or may be having a seizure.” Injectable glucagon has been approved for use in the United States for several decades. Efficacy and safety of glucagon nasal powder to treat severe hypoglycemia was evaluated in two studies of 83 and 70 adults with diabetes. The studies compared a single 3-mg dose of glucagon nasal powder to a single 1-mg dose of I.M. glucagon injection in causing a blood glucose response to insulin-induced hypoglycemia. Glucagon nasal powder adequately increased blood glucose levels. Similar results were observed in a pediatric study of 48 patients with type 1 diabetes who were older than 4 years. In addition, a Phase I study determined that absorption of glucagon nasal powder was not impaired by nasal congestion resulting from the common cold with or without the use of decongestants. Counsel patients and their family members or caregivers on how to recognize the signs and symptoms of severe hypoglycemia and the risks of prolonged hypoglycemia. Tell them to administer a dose of glucagon nasal power by inserting the device tip into one nostril and pressing the plunger all the way in until the green line is no longer showing. Explain that the medication does not need to be inhaled and will work even if the receiver has a cold or is using cold medication. Family members or caregivers should call emergency assistance immediately after administering the dose. If there has been no response after 15 minutes, an additional 3-mg dose may be administered while waiting for emergency assistance. Be sure to explain that each device contains one dose of glucagon and cannot be reused, so they must use a new dispenser if an additional dose is required. When the receiver responds to treatment, the family member or caregiver should provide oral carbohydrates. Glucagon nasal powder (Baqsimi)Manufacturer: Eli LillyDrug class: AntihypoglycemicIndication: Emergency treatment of severe hypoglycemia in patients with diabetes ages 4 years and olderDosage: 3 mg administered as one actuation of the I.N. device into one nostrilOf note: The agent should not be taken by patients with pheochromocytoma (a rare tumor of adrenal gland tissue) or by patients who have insulinoma (a tumor of the pancreas). Manufacturer: Eli Lilly Drug class: Antihypoglycemic Indication: Emergency treatment of severe hypoglycemia in patients with diabetes ages 4 years and older Dosage: 3 mg administered as one actuation of the I.N. device into one nostril Of note: The agent should not be taken by patients with pheochromocytoma (a rare tumor of adrenal gland tissue) or by patients who have insulinoma (a tumor of the pancreas). Explain that the most common adverse reactions associated with glucagon nasal powder are nausea, vomiting, headache, upper respiratory tract irritation, watery eyes, redness of eyes, and itchiness. Adverse effects are similar to those of injectable glucagon, with the addition of nasal and eye-related symptoms (e.g., watery eyes and nasal congestion) because of the way the drug is administered. Inform patients and their family members or caregivers that allergic reactions can occur and to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions. The agent also carries a warning that it should be used with caution by those who have been fasting for long periods, have adrenal insufficiency, or have chronic hypoglycemia, because these conditions result in low levels of releasable glucose in the liver. Patients who are pregnant or plan to become pregnant or are breastfeeding or plan to breastfeed should discuss use with their doctor. Inform patients that it is not known if the agent passes into breast milk.

681-P: Survey of Medical Staff on Use of Glucagon Injection in the Event of Serious Hypoglycemia in Japanese Diabetic Patients—Reason for Poor Spread of Glucagon Use in Japan

Glucagon injection is effective in the event of serious hypoglycemia, especially in unconscious patients who cannot swallow their medications. However, recent surveys in Japan found that only 15.9% of patients have glucagon injections in their possession, and both the adoption rate and the level of awareness in Japan lag behind those of Western countries. This suggests that the medical care and education system for diabetes patients in Japan should deal with this issue not only with patients and their families, but also with healthcare professionals engaged in patient guidance. We carried out a questionnaire survey of the staff at our hospital to determine the state of awareness and provision of glucagon injections by the medical staff in the event of serious hypoglycemia. A questionnaire was distributed to 100 medical staff at our hospital who were engaged in treatment of diabetes, requesting information about the state of knowledge and awareness on glucagon injections. All physicians and about 30% of nurses provided guidance on glucagon injection. In contrast, only a few nutritionists, pharmacists, clinical technologists, and other professionals, who were Certified Diabetes Educators of Japan, had ever done so. We concluded that the lack of knowledge among the medical staff about the technique of glucagon injection and related specific instructions may be one reason for the low rate of glucagon possession and use among the Japanese diabetics. The results suggested that the medical staff have poor knowledge about the technique of injection of glucagon and related instructions, and that a procedure has yet to be established for collection of expired unused dispensed glucagon vials and for re-prescription. Our results highlighted the need for educational programs for a sizeable proportion of healthcare professionals who are involved in the management of diabetes but lack specific information on glucagon injection. Disclosure N. Saito: None. M. Toyoda: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Medtronic Japan Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. M. Kimura: None. M. Fukagawa: Research Support; Self; Kyowa Hakko Kirin Co., Ltd. Speaker's Bureau; Self; Bayer Yakuhin, Ltd., Kissei Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Torii Pharmaceutical Co., Ltd.

965-P: Glucose Sensor Accuracy after Subcutaneous Glucagon Injections Near to Sensor Site

Aim: To compare sensor accuracy (Medtronic Enlite2®) after a subcutaneous (s.c) injection of low-dose glucagon near vs. remote from sensor site. Methods: Twelve adults with type 1 diabetes wore two continuous glucose monitors (CGMglucagon and CGMctrl) placed on each side of the abdomen during two overnight in-clinic visits. CGM values were compared with YSI values. Four hours prior to visit end, a s.c 100 µg glucagon injection was administered 0.2 cm next to the CGMglucagon, and 2 hours later another bolus was injected next to the same sensor. Afterwards, CGM performance was compared with 3-day self-monitoring of blood glucose (SMBG) in free-living conditions. Results: Using YSI as comparator, the overall median absolute relative difference (MARD) for CGMglucagon (N=772) was 17.9% and 14.7% for CGMctrl (N=1352), p=0.15. The percentage of values in zone A+B of Clarke Error Grid Analysis was 96.9% for YSI-CGMglucagon and 97.0% for YSI-CGMctrl, p=0.98. With respect to SMBG, the MARD for CGMglucagon (N=319) was 19.3% and 13.8% for CGMctrl (N=464), p=0.02. The percentage of values in zone A+B for SMBG-CGMglucagon was 94.7% compared to 97.2% for SMBG-CGMctrl, p=0.77. The precision absolute relative deviation between sensors was 16.0%. Conclusion: The study indicates that sensor accuracy may be affected by s.c. glucagon injections near to sensor site compared with distant injections. However, the effect may not be of clinical relevance. Disclosure C. Laugesen: None. S. Schmidt: Speaker's Bureau; Self; Novo Nordisk A/S. R. Tetzschner: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic, Novo Nordisk A/S. Speaker's Bureau; Self; Bayer US, Medtronic, Roche Diabetes Care, Rubin Medical, Sanofi, Zealand Pharma A/S. Stock/Shareholder; Self; Novo Nordisk A/S. A. Ranjan: None. Funding Danish Diabetes Academy

Regulation of Hepatic Follistatin Expression at Rest and during Exercise in Mice.

Follistatin (FST) is a protein with numerous biological roles and was recently identified as an exercise-inducible hepatokine; however, the signals that regulate this are not well understood. The purpose of this study was to delineate potential endocrine factors that may regulate hepatic FST at rest and during exercise. This study used four experiments. First, male and female C57BL/6J mice remained sedentary or were subjected to a single bout of exercise at moderate or exhaustive intensity with liver collected immediately post. Second, mice were injected with glucagon (1 mg·kg, 60 min), epinephrine (2 mg·kg, 30 min), glucagon then epinephrine, or saline. Third, mice were pretreated with propranolol (20-60 mg·kg, 30 min) before epinephrine injection. Fourth, glucagon receptor wild type (Gcgr) or knockout (Gcgr) mice were pretreated with saline or propranolol (20 mg·kg, 30 min) and were subjected to a single bout of exhaustive exercise with liver collected immediately post or after 2 h recovery. In all experiments liver FST mRNA expression was measured, and in experiment four FST protein content was measured. A single bout of treadmill exercise performed at an exhaustive but not moderate-intensity increased FST expression, as did injection of glucagon or epinephrine alone and when combined. Pretreatment of mice with propranolol attenuated the epinephrine-induced increase in FST expression. The exercise-induced increase in FST expression was attenuated in Gcgr mice, with no effect of propranolol. Gcgr mice had higher protein content of FST, but there was no effect of exercise or propranolol. These data suggest that both glucagon and epinephrine regulate hepatic FST expression at rest; however, only glucagon is required for the exercise-induced increase.

High-resolution Mapping of Hyperglycemia-induced Gastric Slow Wave Dysrhythmias.

Background/AimsIt is now recognised that gastric dysrhythmias are best characterised by their spatial propagation pattern. Hyperglycemia is an important cause of gastric slow wave dysrhythmia, however, the spatiotemporal patterns of dysrhythmias in this context have not been investigated. This study aims to investigate the relationship between hyperglycemia and the patterns of dysrhythmias by employing high-resolution (multi-electrode) mapping simultaneously at the anterior and posterior gastric serosa.MethodsHigh-resolution mapping (8 × 16 electrodes per serosal) was performed in 4 anesthetized hounds. Baseline recordings (21 ± 8 minutes) were followed by intravenous injection of glucagon (0.5 mg per dose) and further recordings (59 ± 15 minutes). Blood glucose levels were monitored manually using a glucose sensing kit at regular 5-minute intervals. Slow wave activation maps, amplitudes, velocity, anisotropic ratio, and frequency were calculated. Differences were compared between baseline and post glucagon injection.ResultsBaseline slow waves propagated symmetrically and antegrade. The blood glucose levels were increased by an average of 112% compared to the baseline by the end of the recordings. All subjects demonstrated elevated incidence of slow wave dysrhythmias following injection compared to the baseline (48 ± 23% vs 6 ± 4%, P < 0.05). Dysrhythmias arose simultaneously or independently on anterior and posterior serosa. Spatial dysrhythmias occurred before and persisted after the onset and disappearance of temporal dysrhythmias.ConclusionsInfusion of glucagon induced gastric slow wave dysrhythmias, which occurred across a heterogeneous range of patterns and frequencies. The spatial dysrhythmias of gastric slow waves were shown to be more prevalent and persisted over a longer period of time compared to the temporal dysrhythmias.

Prokinetic effects of spinal cord stimulation and its autonomic mechanisms in dogs.

Spinal cord stimulation (SCS) is widely used to treat chronic pain by inhibiting sympathetic activity; however, it is unknown whether it exerts a prokinetic effect on gastric motility. Our aim was to explore effects and possible mechanisms of SCS on glucagon-induced gastric dysmotility and dysrhythmia. Seven female dogs with electrodes chronically placed on the dorsal column of the spinal cord between T10 and T12 segments were studied in 2 randomized sessions (glucagon+sham-SCS, glucagon+SCS). SCS at T10 using a set of optimized stimulation parameters was performed for 30minute immediately after glucagon injection. The antral manometry, electrogastrogram, and electrocardiogram were recorded to assess gastric contractions, gastric slow waves (GSW), and autonomic functions, respectively. (a) Compared to baseline, glucagon decreased antral motility index (MI) (6315±565 vs 3243±775, P<0.001), reduced the percentage of normal GSW (89±3% vs 58±3%, P<0.01), and increased sympathetic activity (0.25±0 0.06 vs 0.60±0.07, P<0.01). (b) The sympathetic activity was negatively correlated with antral MI (r=-0.558; P<0.01) and the percentage of gastric normal slow wave (r=-0.616; P<0.01). (c) SCS prevented the glucagon-induced impairment in antral hypomotility (MI: 5770±927 vs 5521±1238, P>0.05) and GSW abnormalities (% of normal waves: 84±4% vs 79±6%, P>0.05) and sympathetic activity (0.27±0.03 vs 0.33±0.07, P>0.05). Spinal cord stimulation dramatically improves glucagon-induced impairment in gastric contractions and slow waves by inhibiting sympathetic activity.

Preserved glucose response to low-dose glucagon after exercise in insulin-pump-treated individuals with type 1 diabetes: a randomised crossover study.

This study aimed to compare the increase in plasma glucose after a subcutaneous injection of 200μg glucagon given after 45min of cycling with resting (study 1) and to investigate the effects of glucagon when injected before compared with after 45min of cycling (study 2). We hypothesised that: (1) the glucose response to glucagon would be similar after cycling and resting; and (2) giving glucagon before the activity would prevent the exercise-induced fall in blood glucose during exercise and for 2h afterwards. Fourteen insulin-pump-treated individuals with type 1 diabetes completed three visits in a randomised, placebo-controlled, participant-blinded crossover study. They were allocated by sealed envelopes. Baseline values were (mean and range): HbA1c 54mmol/mol (43-65mmol/mol) or 7.1% (6.1-8.1%); age 45years (23-66years); BMI 26kg/m2 (21-30kg/m2); and diabetes duration 26years (8-51years). At each visit, participants consumed a standardised breakfast 2h prior to 45min of cycling or resting. A subcutaneous injection of 200μg glucagon was given before or after cycling or after resting. The glucose response to glucagon was compared after cycling vs resting (study 1) and before vs after cycling (study 2). The glucose response to glucagon was higher after cycling compared with after resting (mean ± SD incremental peak: 2.6 ± 1.7 vs 1.8 ± 2.0mmol/l, p = 0.02). As expected, plasma glucose decreased during cycling (-3.1 ± 2.8mmol/l) but less so when glucagon was given before cycling (-0.9 ± 2.8mmol/l, p = 0.002). The number of individuals reaching glucose values ≤3.9mmol/l was the same on the 3days. Moderate cycling for 45min did not impair the glucose response to glucagon compared with the glucose response after resting. The glucose fall during cycling was diminished by a pre-exercise injection of 200μg glucagon; however, no significant difference was seen in the number of events of hypoglycaemia. Clinicaltrials.gov NCT02882737 FUNDING: The study was funded by the Danish Diabetes Academy founded by Novo Nordisk foundation and by an unrestricted grant from Zealand Pharma.

Hypoglycemia and Glucagon Utilization in Insulin-Treated Diabetic Patients.

First choice of therapy for severe hypoglycemia outside hospital environment is glucagon injection, an undertaught and underused remedy. Aim of this study was to investigate knowledge about glucagon therapy, possession rate and usage rate in insulin-treated diabetic patients, with special emphasis on history of hypoglycemia and severe hypoglycemia episodes. In this cross-sectional study, 300 insulin-treated diabetic patients (146 males and 154 females, mean age 61.1±16.4 years) were recruited from comprehensive Diabetes Center in Croatia. Specialized self-administered, 13-item questionnaire regarding glucagon therapy and history of hypoglycemia was obtained from each patient, as well as data collected from medical history documentation. Experience of hypoglycemic episode was reported by 233 (77.7%), and severe hypoglycemia by 73 (24.3%) patients. Participants with experience of hypoglycemia have significantly longer diabetes duration (17.2±11.2 vs. 11.9±8.5 years, P<0.001) and lower BMI values (26.38±3.97 vs. 31.11±7.17 kg/m2, P<0.001). Knowledge about glucagon therapy had 55.3% patients, 44.7% obtained it from the pharmacy, while glucagon was used in 35.6% cases of severe hypoglycemia. Glucagon knowledge was better in patients that attended at least one diabetes lecture (P=0.038), while educational level showed no statistical significance (P=0.286). Main significant positive predictor of glucagon knowledge was history of severe hypoglycemia (OR 4.71, 95% CI 1.38 - 16.02, P=0.013). Glucagon therapy was underused in treating severe hypoglycemia. It is highly important to emphasize value of quality education as one of the fundamentals of good diabetes management.

Medical Disimpaction for Children With Organic Esophageal Foreign Body in the Era of Eosinophilic Esophagitis.

Esophageal foreign body impaction (EFBI) is a common presentation in pediatric emergency medicine. Interventions (medical or endoscopic) are often required because of the severity of symptoms and risk of complications. Use of medical disimpaction (MD) such as glucagon injections and effervescent agents (eg, carbonated beverages) has been well described in adults; however, there are limited data in the pediatric literature. Eosinophilic esophagitis (EoE) is a relatively "new" clinicopathological entity that may present with EFBI mostly due to food with histological findings of EoE. Our study aim was to determine the efficacy of MD for organic EFBI in the pediatric population especially in children with EoE. A retrospective chart review was performed using the International Classification of Diseases codes and the emergency department database of patients presenting with EFBI from January 2010 to December 2014. Response to MD was defined as symptomatic relief of obstruction. Age, object ingested, medical agent used, EoE status, complications, and outcome were recorded. A total of 317 presentations of EFBI were identified during the study period, of which organic EFBI accounted for 101 impactions (31.9%). Medical disimpaction was attempted for 42 (41.6%) with organic EFBI, resulting in resolution of symptoms for 16 (38.1%). One child with EoE responded to MD compared with 15 without EoE (4.8% vs 71.4%, P < 0.0001). Medical disimpaction was ineffective in children with EoE but may be of help with symptom resolution in approximately 70% of children without EoE.

Sensor-based wearable system for the detection and automatic treatment of nocturnal hypoglycaemia.

Diabetic patients are prone to daily and severe health-related risks, namely hyper and hypoglycaemia. Hypoglycaemia phenomenon happens when the glucose level in patient's blood is lower than a well-determined sill. It may induce serious impacts, such as functional brain failure or even the death. Hypoglycaemia is especially dangerous when it occurs during the night while the patient is asleep because it becomes difficult to be detected by the patient itself or other persons around him. While all existing sensor-based solutions are detection-only driven, the proposed solution goes beyond and attempts to treat autonomously, and at low cost, the nocturnal hypoglycaemia. The presented system detects the nocturnal hypoglycaemia phenomenon based on accelerated heart-rate symptom and a progressive detection algorithm. The system treats then the detected nocturnal hypoglycaemia throughout safe and automatic injection of glucagon.

Intraperitoneal, subcutaneous and intravenous glucagon delivery and subsequent glucose response in rats: a randomized controlled crossover trial

ObjectiveHypoglycemia is a frequent and potentially dangerous event among patients with diabetes mellitus type 1. Subcutaneous glucagon is an emergency treatment to counteract severe hypoglycemia. The effect of intraperitoneal glucagon...

A Hepatocyte FOXN3-α Cell Glucagon Axis Regulates Fasting Glucose

The common genetic variation at rs8004664 in the FOXN3 gene is independently and significantly associated with fasting blood glucose, but not insulin, in non-diabetic humans. Recently, we reported that primary hepatocytes from rs8004664 hyperglycemia risk allele carriers have increased FOXN3 transcript and protein levels and liver-limited overexpression of human FOXN3, a transcriptional repressor that had not been implicated in metabolic regulation previously, increases fasting blood glucose in zebrafish. Here, we find that injection of glucagon into mice and adult zebrafish decreases liver Foxn3 protein and transcript levels. Zebrafish foxn3 loss-of-function mutants have decreased fasting blood glucose, blood glucagon, liver gluconeogenic gene expression, and α cell mass. Conversely, liver-limited overexpression of foxn3 increases α cell mass. Supporting these genetic findings in model organisms, non-diabetic rs8004664 risk allele carriers have decreased suppression of glucagon during oral glucose tolerance testing. By reciprocally regulating each other, liver FOXN3 and glucagon control fasting glucose.

The Postprandial C-peptide–to–Glucose Ratio Correlated with Beta-Cell Function in Japanese Patients with Type 2 Diabetes Mellitus

The onset of type 2 diabetes mellitus(T2DM) is based on the insulin resistance and decreasing of insulin secretion. Residual β-cell function is a key factor in achieving optimal glycemic control in patients with type 2 diabetes. Glucagon induces insulin secretion by direcdtly stimulating β-cells, therefore glucagon stimulaton test(GST) is a reliable marker for β-cell function. Fasting C-peptide(CPR)-index(CPR[ng/ml] to glucose[mg/dl] ratio x100; F-CPRI) is used as a marker of insulin secretion. We evaluated the efficacy of postprandial CPR to glucose ratio(P-CPRI) as a tool for evaluating β-cell function. Japanese T2DM patients with inadequte glycemic control(HbA1c&amp;gt;7.0%) were enrolled in the study(n=333, insulin therapy =217). HbA1c, fasting CPR and glucose were measured, and F-CPRI was calculated. Postprandial(120 min after breakfast) CPR and glucose were measured, and P-CPRI was calculated. For the GST, CPR was determinated before and 6 min after 1mg of glucagon injection. GSTδCPR(CPR[6 min] - CPR[0 min]) was calculated. Factors correlated with GSTδCPR were analyzed using simple and multiple stepwise regression analysis. P value&amp;lt;0.was defined as statistically different. F-CPR-index, P-CPR-index and GSTδCPR were 1.42±0.85, 2.26±1.59 and 1.85±1.15, respectively. Simple regression analysis showed that GSTδCPR was significantly correlated with age, height, body weight(BW), BMI, gender, duration of diabetes, diebetic retinopathy, diabetic nephropathy, insulin therapy, F-CPRI and P-CPRI. Multiple stepwise regression analysis revealed that independent factors contributing to GSTδCPR were BW(β=0.331, p&amp;lt;0.001), P-CPRI(β=0.451, p&amp;lt;0.001), duration of diabetes(β= -0.104, p=0.025), diabetic retinopathy(β= -0.127, p=0.004), DPP-4 inhibitor(β= -0.089, p=0.036) and biguanide(β= -0.144, p=0.001). Our date demonstrated that P-CPRI was valuable in assessing β-cell function and can help clinicians in clinical practice. Disclosure Y. Matsuhashi: None. S. Chikazawa: None. H. Nakayama: None. M. Murabayashi: None. S. Mizushiri: None. S. Osonoi: None. K. Takahashi: None. H. Otaka: None. M. Yanagimachi: None. H. Murakami: None. M. Daimon: None.

Inadequate Use of Glucagon in Patients with T1D

Glucagon is an invaluable tool for patients with type 1 diabetes (T1D) who experience severe hypoglycemia, but little is known about the actual use of glucagon in this patient population. This study was undertaken among individuals with T1D or caregivers to assess the perceptions and/or past experiences using the currently available glucagon rescue kits, and factors that might increase its utility in the management of T1D. Survey responses from 264 adults with T1D (mean age 41.2 years [SD 15.5]) and 58 caregivers of a person with T1D (mean age 11.8 years [SD 3.7]) were included in the analyses. Overall the participants were highly educated, predominantly covered by private health insurance, and the majority were on insulin pumps. The survey revealed that the majority of the individuals with T1D had been prescribed glucagon; however, almost a third of the adult patients did not receive any education on its use, and a third of the adult patients did not have a current prescription. Caregivers reported higher percentages of receiving education on glucagon use and also having a current prescription. Of those with severe hypoglycemia who had glucagon available, half did not receive a glucagon injection. The majority of patients who had received glucagon injection reported various problems with the procedure; those who did not receive glucagon injection reported a number of barriers to its use. These data strongly suggest the need for 1) standards of practice that would increase prescribing of glucagon 2) initial and ongoing education on its use and administration 3) development of a glucagon rescue option that would eliminate the complexity relating to current formulations and packaging of rescue glucagon kits. Disclosure M.W. Haymond: Advisory Panel; Self; Zealand Pharma A/S. Other Relationship; Self; Xeris Pharmaceuticals, Inc.. J. Liu: None. J. Bispham: None. A. Hickey: None. A.H. McAuliffe-Fogarty: Advisory Panel; Self; Novo Nordisk Inc..