Glucagon Injection Research Articles

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..

Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: A randomized prospective pilot study

AimsWe examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal) is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM) without severe insulin deficiency as determined by glucagon stimulation. MethodsFifty patients receiving BBIT were enrolled in this 24-week, prospective, randomized, open-labeled study. After excluding subjects with fasting C-peptide immunoreactivity (CPR) < 1.0 ng/mL and CPR increase < 1.0 ng/mL at 6 min post glucagon injection, 25 were randomly allocated to receive Lira-basal (n = 12) or continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight (BW), 7-point self-monitored blood glucose (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores. ResultThe Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group showed no change. BW was reduced in the Lira-basal group but increased in the BBIT group. The Lira-basal group also exhibited significantly reduced pre-breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but not the BBIT group. Plasma lipids, liver function, and kidney function were not significantly changed in either group. ConclusionsLira-basal therapy is superior to BBIT for T2DM without severe insulin deficiency.This study was registered with UMIN Clinical Trials Registry (UMIN000028313).

Design of Switched Model Predictive Control Algorithms for a Dual-Hormone Artificial Pancreas

Abstract In this paper, we evaluate the closed-loop performance of two switching strategies for a dual-hormone artificial pancreas (AP). The dual-hormone AP administers insulin and glucagon subcutaneously. Since insulin and glucagon have opposite effects, we want to avoid simultaneous injections of these two hormones. To handle non-simultaneous injections of insulin and glucagon, we compare model predictive control (MPC) algorithms using a hysteresis switch between insulin and glucagon controllers with a multiple-input single-output (MISO) formulation. Although the closed-loop performance of these two control strategies is similar, the hysteresis switch is preferable due to (i) its greater flexibility in control design and tuning and (ii) a more straightforward way to avoid simultaneous injections of insulin and glucagon.

Effect of circulating glucagon and free fatty acids on hepatic FGF21 production in dairy cows.

Modern dairy cows meet the energy demand of early lactation by calling on hormonally driven mechanisms to increase the use of lipid reserves. In this context, we recently reported that fibroblast growth factor-21 (FGF21), a hormone required for efficient use of lipid reserves in rodents, is upregulated in periparturient dairy cows. Increased plasma FGF21 in early lactation coincides with elevated circulating concentrations of glucagon (GCG) and nonesterified fatty acids (NEFA). To assess the relative contribution of these factors in regulating FGF21, two experiments were performed in energy-sufficient, nonpregnant, nonlactating dairy cows. In the first study, cows were injected with saline or GCG every 8 h over a 72-h period. GCG increased hepatic FGF21 mRNA by an average of fivefold over matched controls but had no effect on plasma FGF21. In the second study, cows were infused and injected with saline, infused with Intralipid and injected with saline, or infused with Intralipid and injected with GCG. Infusions and injections were administered intravenously over 16 h and subcutaneously every 8 h, respectively. Intralipid infusion increased plasma NEFA from 92 to 550 µM within 3 h and increased plasma FGF21 from 1.3 to >11 ng/ml 6 h later; FGF21 mRNA increased by 34-fold in liver but remained invariant in adipose tissue. GCG injections during the Intralipid infusion had no additional effects on plasma NEFA, liver FGF21 mRNA, or plasma FGF21. These data implicate plasma NEFA as a key factor triggering hepatic production and increased circulating concentrations of FGF21 in early lactation.

Normal meal tolerance test is preferable to the glucagon stimulation test in patients with type 2 diabetes that are not in a hyperglycemic state: Comparison with the change of C-peptide immunoreactivity.

Aims/IntroductionThe aim of the present study was to evaluate the properties of the glucagon stimulation test (GST) and the normal meal tolerance test (NMTT) in patients with type 2 diabetes.Materials and MethodsWe enrolled 142 patients with type 2 diabetes, and carried out a GST and a NMTT. We carried out the NMTT using a calorie‐controlled meal based on an intake of 30 kcal/kg ideal bodyweight/day. We calculated the change in C‐peptide immunoreactivity (ΔCPR) by subtracting fasting CPR from the CPR 6 min after the 1‐mg glucagon injection (GST) or 120 min after the meal (NMTT).ResultsMean ΔCPR for the GST was 2.0 ng/mL, and for the NMTT was 3.1 ng/mL. A total of 104 patients had greater ΔCPR in the NMTT than the GST, and the mean ΔCPR was significantly greater in the NMTT than the GST (P < 0.05). To exclude any influence of antidiabetic drugs, we examined 42 individuals not taking antidiabetic agents, and found the mean ΔCPR was significantly greater in the NMTT than the GST (GST 2.4 ng/mL, NMTT 4.3 ng/mL; P < 0.05). To consider the influence of glucose toxicity, we carried out receiver operating characteristic analyses with fasting plasma glucose and glycated hemoglobin. The optimal cut‐off levels predicting GST ΔCPR to be larger than NMTT ΔCPR were fasting plasma glucose 147 mg/dL and glycated hemoglobin 9.0% (fasting plasma glucose: sensitivity 0.64, specificity 0.76, area under the curve 0.73; glycated hemoglobin: sensitivity 0.56, specificity 0.71, area under the curve 0.66).ConclusionsThe NMTT is a reliable insulin secretion test in patients with type 2 diabetes, except for those in a hyperglycemic state.

Case 2: Prolonged Hypoglycemia in an Adolescent without Diabetes

1. Akshay Sharma, MBBS* 2. Irene Hong-McAtee, MD† 1. *St Jude Children's Research Hospital, Memphis, TN. 2. †Division of Endocrinology and Diabetes, Vanderbilt University School of Medicine, Nashville, TN. A 16-year-old girl who has no contributory past medical history suddenly starts experiencing generalized weakness and drowsiness. In the emergency department, her finger stick blood glucose (BG) is 22 mg/dL (1.2 mmol/L) (fasting reference range 70–99 mg/dL [3.9–5.5 mmol/L]). She is given 160 mL of 12.5% dextrose intravenously (IV) and is admitted to the pediatric intensive care unit (PICU) for monitoring and further management. On arrival to the PICU, her vital signs show sinus tachycardia (heart rate of 118 beats per minute). Her weight is 38.9 kg and height is 144.7 cm (both below the 3rd percentile). Her physical examination findings are otherwise unremarkable. Her basic metabolic profile and complete blood cell count do not reveal any abnormalities except a low BG. Blood is collected to measure serum insulin, C-peptide, proinsulin, β-hydroxybutyric acid, and ketones when her BG concentration decreases to less than 50 mg/dL (2.8 mmol/L) in the PICU. She is given 12.5% dextrose multiple times as well as a glucagon injection once for BG less than 50 mg/dL (2.8 mmol/L) (Figure). Strikingly, she does not display any other symptoms until her BG decreases to less than 20 mg/dL (1.1 mmol/L). At one point her BG reaches 12 mg/dL (0.7 mmol/L) and she develops diaphoresis but she still remains conversational. Her urine drug screen is negative for any oral hypoglycemic agents. Corticotropin and glucagon stimulation tests as well as …

Care of the Athlete with Diabetes

Care of the Athlete with Diabetes

Changes in portal vein flow mean velocity after glucagon application measured by magnetic resonance imaging flowmetry indicates presence of severe sinusoidal injury in patients with colorectal liver metastases

Aims: Non-invasive methods like aspartate aminotransferase to platelets ratio index (APRI) score or spleen volume changes were proposed to identify patients with sinusoidal injury after preoperative chemotherapies for colorectal liver metastases. Magnetic resonance imaging flowmetry can be used to measure changes in portal vein hemodynamics in patients with sinusoidal injury. The present study evaluates the changes in portal vein flow mean velocity (VELO) after glucagon application and analyzes their ability to predict severe sinusoidal injury (SSI) in comparison to other methods. Methods: Magnetic resonance imaging flowmetry of portal vein was estimated in 28 fasting patients and repeated five minutes after 0.5 mg glucagon injection the day before liver surgery. APRI score was estimated the same day. Spleen volume changes were calculated from segmented spleen volumes on imaging before chemotherapy start and the day before surgery. Resected non-tumorous liver parenchyma was evaluated for sinusoidal injury; parenchymal extinction lesion or nodular regenerative hyperplasia was recognized as SSI. Results: SSI was observed in 6 of 28 patients. Patients with SSI demonstrated higher APRI score 0.65 vs. 0.36, p = 0.028; and non-significant change in spleen volume, 36% vs. 12%, p = 0.764. Percentage of change in VELO five minutes after glucagon in SSI patients was 11% vs. – 3%, p = 0.039. Change in VELO <= – 0.5% predicted SSI with 83% sensitivity and 73% specificity (cross-validated classification error rate 29%), similarly to APRI score >=0.43 with the same sensitivity and specificity but higher classification error rate 32%. Conclusions: Relative changes of VELO five minutes after glucagon administration showed lowered ability of portal system to react on glucagon stimuli in patients with SSI. Application of glucagon as a stress test of portal vein hemodynamic facilitates magnetic resonance imaging flowmetry ability to predict SSI non-invasively.

Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance.

ObjectiveGlucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown.MethodsGlucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot.ResultsThe central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca2+-calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK)-dependent mechanism. More specifically, the central injection of glucagon increases PKA activity and reduces protein levels of CaMKKβ and its downstream target phosphorylated AMPK in the hypothalamic arcuate nucleus (ARC). Consistently, central glucagon significantly decreased AgRP expression. Inhibition of PKA and genetic activation of AMPK in the ARC blocked glucagon-induced anorexia in lean rats. Genetic down-regulation of glucagon receptors in the ARC stimulates fasting-induced hyperphagia. Although glucagon was unable to decrease food intake in DIO rats, glucagon sensitivity was restored after inactivation of CaMKKβ, specifically in the ARC. Thus, glucagon decreases food intake acutely via PKA/CaMKKβ/AMPK dependent pathways in the ARC, and CaMKKβ mediates its obesity-induced hypothalamic resistance.ConclusionsThis work reveals the molecular underpinnings by which glucagon controls feeding that may lead to a better understanding of disease states linked to anorexia and cachexia.

Efficacy of Endoscopic Interventions for Esophageal Foreign Body Removal at Tertiary Care Center

Introduction: Foreign body (FB) ingestion is a common indication for endoscopic intervention. While a majority of accidentally ingested foreign bodies pass spontaneously, endoscopy is required in up to 76% patients in with intentional ingestions. Need for surgical intervention in difficult cases is quoted to be as high as 16%. The primary aims of this study are to analyze the techniques and efficacy of endoscopic intervention in esophageal FB removal at a tertiary care center. Methods: All patients above 18 years of age admitted with a diagnosis of esophageal FB between 1/1/2010 to 12/31/2013 were included in study. Using electronic health records data on patient demographics, co-morbidities, type and location of FB, use of glucagon, endoscopic procedure details and need for surgical intervention were collected. Statistical analysis was performed using unpaired t test, fisher's exact test and chi-square test. Results: A total of 125 patients were enrolled. Average age for our patient population was 42.08 years. 72% were males, 38% patients were active smokers and 29% patients consumed alcohol. Lower 1/3 of esophagus was most common site of impaction (37% cases). Glucagon was tried in 49 (39%) patients with food impaction and relieved symptoms in 15 patients (30% success rate) averting need of urgent endoscopy. In remaining 110 patients, 72 (65%) patients had food impaction, 24(22%) patients had blunt FB and 14 (13%) had sharp FB impaction. FB was successfully removed in 89 patients (81%) via endoscopy. Success rate were found to differ based on type of FB (significantly higher for food bolus (94%, OR-12, P - 0.001) as compared to blunt (67%) or sharp objects (43%). Endoscopic removal was more successful for impacted FB in lower 1/3 of esophagus, (OR-11 P - 0.008) and if the underlying etiology was schatzki ring or stricture (OR - 6.23, P < 0.05) as compared to normal appearing esophagus. Most commonly used instruments for FB removal included snare, rothnet and rat tooth/ alligator forceps. Rigid upper endoscopy was required in 5 cases and only 4 patients underwent surgical exploration to remove FB after attempt at endoscopic retrieval was unsuccessful. Conclusion: Flexible upper endoscopy is an effective modality esophageal FBs removal. Glucagon injection should be offered first line to all patients with food impaction on a regular basis (unless contraindicated) as a safe option and can obviate the need for unnecessary emergent EGD.

Journal of Diabetes News

Journal of Diabetes News

Hyperglycemia-induced small intestinal dysrhythmias attributed to sympathovagal imbalance in normal and diabetic rats.

Hyperglycemia is known to induce dysrhythmias in the stomach; however, it is unknown whether they are also induced in the small intestine. Autonomic dysfunction is commonly noted in diabetes but the role it plays in hyperglycemia-induced dysrhythmias remains unknown. This study aimed to explore the effects of hyperglycemia on intestinal myoelectrical activity and the role of autonomic functions in hyperglycemia. Small intestinal myoelectrical activity (slow wave and spike activity) and autonomic functions (assessed by the spectral analysis of heart rate variability) were measured in Goto-Kakizaki diabetic rats and control rats treated with acute glucagon. Blood glucose was measured and its correlation with intestinal slow waves was determined. (1) The diabetic rats showed reduced regularity in intestinal slow waves in fasting and fed states (p < 0.001 for both), and increased sympathovagal balance (p < 0.05) in comparison with the control rats. The regularity in intestinal slow waves was negatively correlated with the HbA1c level in all rats (r = -0.663, p = 0.000). (2) Glucagon injection in the control rats induced transient hyperglycemia, intestinal slow wave dysrhythmias and impaired autonomic functions, similar to those observed in the diabetic rats. The increase in blood glucose was correlated with the decrease in the regularity of intestinal slow waves (r = -0.739, p = 0.015). Both spontaneous and glucagon-induced hyperglycemia results in slow wave dysrhythmias in the small intestine. Impairment in autonomic functions (increased sympathovagal balance) may play a role in hyperglycemia-induced dysrhythmias.

Case study: hidden complexity of medicines use: information provided by a person with intellectual disability and diabetes to a pharmacist

Accessible summaryA pharmacist spoke to people with intellectual disabilities about their medicines.One person with diabetes found it hard to manage. He had to inject insulin. He had to take tablets that were in a blister pack. He did not like having diabetes and was distressed. He did not store his insulin properly. He often had low sugar and had to get a glucagon injection. Pharmacists can help people who have diabetes. They can give advice about medicines. They can give advice about injecting and storing insulin. People should only ask for more insulin and medicines from the pharmacy when they need them.SummaryPeople with intellectual disabilities may be ‘invisible’ to pharmacists. They are a complex group of patients many of whom have diabetes. Pharmacists may have little experience of the challenges faced by this high risk group of patients who may be prescribed high risk medications. This case report details information supplied by Pat, a 33 year old gentleman with intellectual disabilities and diabetes to a pharmacist researcher. The aim of the research project, which received ethics approval from a university research ethics committee, was to determine the views and knowledge of people with intellectual disabilities about medication use. Pat proved to be an excellent source of information concerning the complexity of ‘self care’ by a person with intellectual disabilities and diabetes. Many quality issues became evident to the pharmacist researcher during the interview. These issues included ‘self care’, diabetes distress, health literacy, medication information provision, safe practices around storage of insulin and glucagon, appropriateness of a monitored dosage system, repeat dispensing of insulin and the complexity of care co‐ordination. The international trend to deinstitutionalise the care of people with intellectual disabilities will require that this complex group of patients to get support from care givers and health and social care professionals in the community setting to ensure quality medication use. Pharmacists must rise to challenge to provide accessible patient centred pharmaceutical care to this high risk population.

Glucagon directly interacts with vagal afferent nodose ganglion neurons to induce Ca2+ signaling via glucagon receptors

Glucagon is released from the pancreatic islets postprandially and under hypoglycemic and cold conditions, and regulates glucose metabolism, feeding, energy expenditure and heat production, the functions partly controlled by the brain. Peripheral glucagon could signal to the brain via passing through the blood–brain barrier and/or acting on the vagal afferent. However, the latter remains to be determined. The present study aimed to clarify whether glucagon directly interacts with the nodose ganglion (NG) neurons of vagal afferent nerves in mice. In vivo study showed that intraperitoneal injection of glucagon induced phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2), cellular activation makers, in NG neurons. In fura-2 microfluorometric studies, glucagon increased cytosolic Ca2+ concentration ([Ca2+]i) in single NG neurons. The glucagon-induced [Ca2+]i increases were suppressed by a glucagon receptor antagonist, des-His1-[Glu9]-Glucagon (1–29) amide, and the glucagon receptor mRNA was expressed in NG neurons. The majority of glucagon-responsive NG neurons exhibited [Ca2+]i responses to insulin and cholecystokinin-8, the hormones that are secreted postprandially and implicated in satiety. These results demonstrate that glucagon, by interacting with the glucagon receptor, directly activates vagal afferent nerves, possibly being relayed to the signaling to the brain and formation of satiety.

Potential risks of glucagon stimulation test in elderly people

The glucagon stimulation test (GST) is a reliable measure for assessing growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion. The GST is considered to be a safe test, with few mild side effects, especially in adults and in the elderly in whom underlying co-morbidities may be present. ObjectiveTo describe the side effects of the GST in elderly people. Design and settingThe study was performed with patients of the geriatric ambulatory of our hospital who were recruited to voluntarily participate in a research study concerning the GH and ACTH axis in the elderly people. Forty-two subjects (n=5 males and 37 females) aged 67–88 years, without hypothalamic–pituitary disease, were submitted to the GST. The GST was performed by intramuscular injection of 1mg of glucagon. Blood samples were collected at baseline, and 90, 120, 150, and 180min after glucagon injection for GH and cortisol measurements. ResultsDuring the test, 9 subjects (21.4%) had side effects, which included: nausea (14.2%), indisposition (11.9%), hypotension (9.5%), vomiting (7.1%), sweating (4.7%), and dizziness (2.3%). There were four cases of severe symptomatic hypotension, with inaudible blood pressure in two cases. In one case of severe hypotension, the subject suffered two episodes of generalized tonic seizures. Patients who had side effects at GST had statistically higher peak of cortisol (28.9±6.67μg/dL) and a statistical trend to higher GH peak (8.74±5.96μg/L). In the group of patients who did not have side effects, the mean cortisol and GH peak were 19.05±5.36μg/dL and 5.32±3.52μg/L, respectively. ConclusionAlthough the GST is a reliable alternative test to the ITT, it should be cautiously used in the elderly because this population may have co-morbidities including vascular and cardiac diseases that could be potentiated with side effects of the test, such as severe hypotension.

Conditional glucagon receptor overexpression has multi-faceted consequences for beta-cell function

BackgroundAlthough it is known that the islet expression of glucagon receptors is increased in type 2 diabetes, its implication for beta-cell function is not known. ObjectiveTo determine whether increased beta cell glucagon receptor expression and action influences multiple aspects of beta cell function. Materials/methodsMice with beta cell specific overexpression of the glucagon receptor (RIP-Gcgr) were subjected to intravenous glucose tolerance tests with acute injections of glucagon or GLP-1. Mice were also subjected to intravenous arginine and carbachol tests and insulin secretory responses were evaluated. ResultsThe specific beta-cell overexpression of glucagon receptors has a complex and diverse consequence with dissociated consequences on beta-cell secretion depending on the stimulatory secretagogue in that whereas the potentiating effects of GLP-1 and arginine on glucose-stimulated insulin secretion were completely lost, the response to the muscarinic receptor agonist carbachol was largely unaffected and the insulin secretory response to glucose was exaggerated. ConclusionThis suggests that glucagon receptor overexpression, which is seen in hyperglycemia, may have dissociated consequence on beta cell function in its regulation under fasting, after meal and in response to autonomic nervous activation.

Treating severe hypoglycemia: rapid mixing of lyophilized glucagon and diluent at point of care with the Enject GlucaPen.

Severe hypoglycemia (SH) is a common problem in type 1 diabetes (T1D). Annually, nearly 1 of 5 persons with long-standing T1D will have SH. Though injections of glucagon are effective in treating SH, liquid formulations of glucagon are biochemically very unstable. For this reason, available preparations of glucagon are lyophilized; the powder and the diluent must be mixed at the point of care prior to administration and any remaining drug must be discarded. The process of mixing and delivery is complex. Coupled with the emotional stress of the caregiver, errors in glucagon delivery are very common. For these reasons, workers at Enject, Inc are in the process of developing a device that addresses the shortcomings of this currently approved method of glucagon delivery. The Enject device will store the glucagon powder and the diluent in separate compartments and will rapidly mix and inject the components only upon activation of the pen at the point of care.

Advanced Clinical Interventions Performed by Emergency Medical Responder Firefighters prior to Ambulance Arrival

Introduction. Data on the clinical interventions performed by emergency medical responder firefighters (EMRFs) are limited outside the context of cardiac arrest. We sought to understand the broader medical role of firefighters by examining fire-ambulance arrival order and documenting specific interventions provided by firefighters with advanced EMR training. Methods. A secondary analysis was conducted using electronic patient care records from a single ambulance service and two municipal fire departments that partner to provide emergency response in two suburbs of Minneapolis, Minnesota. Firefighters in both municipalities are dispatched to all medical calls, regardless of severity, and receive training in the following advanced EMR skills: intravenous line placement, administration of oral nitroglycerin and aspirin, placement of supraglottic airways, administration of albuterol via nebulizer, and injections of intramuscular glucagon and epinephrine. Time stamps for unit arrival on scene were used to determine arrival order and to quantify fire lead time (i.e., the interval EMRFs were on scene before paramedics). Results. Fire and ambulance records were linked for 10,403 patient encounters that occurred over 2.5 years. EMRFs arrived first in 9,001 calls (88%) with an average fire lead time of 4.5 minutes. In the two communities, firefighters performed at least one of the six advanced training interventions in 688 patient encounters (7.6%) when they reached the patient first, the most frequent being intravenous line placement (n = 340; 3.8%) and administration of oral nitroglycerin or aspirin (n = 303; 3.4%). EMRFs arrived first to 96 cases of cardiac arrest and performed chest compressions in 78%, automated external defibrillator use in 44%, supraglottic airway placement in 32%, and intravenous line starts in 18%. A modest positive association was observed between increasing fire lead time and use of cardiac arrest interventions by EMRFs. Conclusions. EMRFs performed advanced EMR training interventions in a small fraction of the patients they were able to reach before paramedics, and further study of the clinical significance of these interventions in the hands of this responder group is needed. EMRF training in these communities should continue to emphasize the fervent and consistent application of BLS resuscitation interventions in victims of cardiac arrest.

Abnormal Sensitivity to Glucagon and Related Peptides in Primary Adrenal Cushing's Syndrome.

Illegitimate G-protein coupled receptors are known to control cortisol secretion in adrenal adenomas and bilateral macronodular adrenal hyperplasias (BMAHs) causing Cushing's syndrome. In the present study, we have evaluated the role of glucagon in the regulation of cortisol secretion in 13 patients with BMAH or adrenocortical adenoma causing subclinical or overt Cushing's syndrome. Injection of glucagon provoked an increase in plasma cortisol in 2 patients. After surgery, immunohistochemical studies showed the presence of glucagon receptor-like immunoreactivity in clusters of spongiocytic cells in adrenal tissues from patients who were sensitive in vivo to glucagon. We also observed an in vitro cortisol response to vasoactive intestinal peptide from an adenoma, which was insensitive to glucagon and pituitary adenylate cyclase-activating peptide. Altogether, our data show that ectopic glucagon receptors are expressed in some adrenal cortisol-producing benign lesions. Our results also indicate that circulating glucagon may influence cortisol release under fasting conditions.

Modeling and qualitative analysis of diabetes therapies with state feedback control

For the therapies of diabetes mellitus, a novel mathematical model with two state impulses: impulsive injection of insulin and impulsive injection of glucagon, is proposed. To avoid hypoglycemia and hyperglycemia, the injections of insulin and glucagon are determined by closely monitoring the plasma glucose level of the patients. By using differential equation geometry theory, the existence of periodic solution and the attraction region of the system have been obtained, which ensures that injections in such an automated way can keep the blood glucose concentration under control. The simulation results verify that the better insulin injection strategy in closed-loop control is a larger dose but longer interval rather than a smaller dose but shorter interval. Besides, our numerical analysis reveals that medicine studies and practice that slow down the insulin degradation are helpful for the plasma glucose control. Our findings can provide significant guidance in both design of artificial pancreas and clinical treatment.