Intravenous Glucagon Research Articles

Mechanoreceptors of the Proximal Stomach and Perception of Gastric Distension

To assess the role of tension receptors in gastric perception by pharmacologically modifying gastric contractile activity during isovolumetric distensions of the proximal stomach with the hypothesis that relaxation decreased perception and contraction increased it. Fourteen healthy subjects underwent two 30-min isovolumetric (75% of the threshold volume for discomfort) distensions using a barostat. During the second distension, either gastric relaxation was induced by intravenous (i.v.) glucagon 4.8 microg/kg bolus plus 9.6 microg/kg per h or contraction by i.v. erythromycin 3 mg/kg. Hunger and fullness were assessed with a 100-mm analog scale before and at 15 and 30 min during each distension. Glucagon decreased baseline intrabag pressure (8.4 +/- 1.0 vs 10.7 +/- 1.3 mmHg; p < 0.05) and abolished the pressure waves (0 vs 16.7 +/- 2.3) when compared with placebo, whereas erythromycin increased baseline pressure (13.2 +/- 1.0 vs 11.9 +/- 0.9 mmHg; p < 0.05) and the rate of pressure waves (31.7 +/- 5.4 vs 20.5 +/- 3.1; p < 0.05). Fullness increased (p < 0.05) during distension, but it was unaffected by either of the drugs: Delta score (i.e., score during distension--baseline score) of 38 +/- 10 mm (glucagon) versus 22 +/- 10 (placebo) and 24 +/- 17 mm (erythromycin) versus 36 +/- 14 (placebo) at 15 min. Similar observation were made at 30 min. Hunger was influenced neither by distension nor by any of the two drugs consistently. Our data do not support a prominent role of tension receptors of the proximal stomach on perception of fullness, suggesting that stretch, that is, volume, is the more relevant stimulus.

Calcium Channel Blocker Ingestion: An Evidence-Based Consensus Guideline for Out-of-Hospital Management

In 2003, U.S. poison control centers were consulted after 9650 ingestions of calcium channel blockers (CCBs), including 57 deaths. This represents more than one-third of the deaths reported to the American Association of Poison Control Centers' Toxic Exposure Surveillance System database that were associated with cardiovascular drugs and emphasizes the importance of developing a guideline for the out-of-hospital management of calcium channel blocker poisoning. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with suspected ingestions of calcium channel blockers. An evidence-based expert consensus process was used to create this guideline. This guideline applies to ingestion of calcium channel blockers alone and is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. The panel's recommendations follow. The grade of recommendation is in parentheses. 1) All patients with stated or suspected self-harm or the recipient of a potentially malicious administration of a CCB should be referred to an emergency department immediately regardless of the amount ingested (Grade D). 2) Asymptomatic patients are unlikely to develop symptoms if the interval between the ingestion and the call is greater than 6 hours for immediate-release products, 18 hours for modified-release products other than verapamil, and 24 hours for modified-release verapamil. These patients do not need referral or prolonged observation (Grade D). 3) Patients without evidence of self-harm should have further evaluation, including determination of the precise dose ingested, history of other medical conditions, and the presence of co-ingestants. Ingestion of either an amount that exceeds the usual maximum single therapeutic dose or an amount equal to or greater than the lowest reported toxic dose, whichever is lower (see Table ), would warrant consideration of referral to an emergency department (Grade D). 4) Do not induce emesis (Grade D). 5) Consider the administration of activated charcoal orally if available and no contraindications are present. However, do not delay transportation in order to administer charcoal (Grade D). 6) For patients who merit evaluation in an emergency department, ambulance transportation is recommended because of the potential for life-threatening complications. Provide usual supportive care en route to the hospital, including intravenous fluids for hypotension. Consider use of intravenous calcium, glucagon, and epinephrine for severe hypotension during transport, if available (Grade D). 7) Depending on the specific circumstances, follow-up calls should be made to determine outcome at appropriate intervals based on the clinical judgment of the poison center staff (Grade D).

The Effect of Prematurity and Intrauterine Growth Restriction on Glucose Metabolism in the Newborn

After completing this article, readers should be able to: 1. List the three components required for the transition to independent glucose homeostasis in the newborn. 2. Explain why preterm infants are at increased risk for neonatal hypoglycemia. 3. Compare the capacity for gluconeogenesis in the term and preterm infant and in the infant who has intrauterine growth restriction. 4. Describe the effects of enteral feedings on glucose homeostasis in the newborn. At birth, the transplacental supply of nutrients, especially glucose, to the newborn is interrupted abruptly. This sets into motion a complex cascade of metabolic and endocrine events that allow a healthy term newborn to adjust to his or her new environment. This cascade is triggered by a surge in the concentrations of glucagon and catecholamines and cessation of insulin secretion. Glucagon and catecholamines increase glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis. The complex enzyme machinery responsible for these processes is mature in term healthy newborns. In contrast, the metabolic and endocrine processes allowing the transition to the extrauterine environment are not developed fully in preterm infants and those who have suffered intrauterine growth restriction (IUGR), placing these newborns at significant risk of hypoglycemia. This review focuses on the regulation of glucose metabolism during the fetal period and the metabolic and endocrine changes that occur at birth and in the postnatal period, with special reference to preterm infants and infants who have experienced IUGR. Carbohydrate is transported to the fetus as glucose, which is taken up from the maternal plasma by glucose transporters. GLUT1 and GLUT3 are the primary glucose transporters involved in the transplacental movement of glucose and are present on both the microvillus and basal membranes of the syncytial barrier. Glucose is transported to the fetus by facilitative diffusion according to concentration-dependent kinetics, with placental glucose transport capacity increasing with gestational age. The …

Islet autotransplantation combined with pancreatectomy for treatment of pancreatic adenocarcinoma: a case report

Extensive pancreatectomy (EP) may increase the resection rate of pancreatic adenocarcinoma (PA). Unfortunately, EP often results in unstable diabetes. Recently, islet autotransplantation (auto-Tx) has offered the potential to prevent this metabolic disorder. Because of the fear of contamination of prepared islets by malignant cells, this procedure has so far not been used as a treatment for PA. We herein report a case of a 63-year-old nondiabetic patient who underwent EP combined with islet auto-Tx in an emergency operation following histologically proved R 0-resection for PA (pT 3pN 1G 2). Islets were isolated from the excised pancreas using a continuous digestion filtration device. The resultant preparation was injected into the portal vein. Owing to the moderate fasting hyperglycemia, postoperative exogenous insulin therapy was necessary (26 U/d). After discharge, the patient's daily insulin dose was gradually reduced. At 1-year follow-up the fasting C-peptide level was 0.66 ng/mL, and an oral glucose tolerance test (oGTT) and an intravenous (IV) glucagon stimulation (GS) showed functioning engrafted islets. The K- ras mutations were detected in the paraffin-embedded PA, but not in the prepared islets or in the peripheral blood. Computed tomographic (CT) imaging revealed neither local tumor recurrence nor liver metastases. At 2-year follow-up, the patient was on a balanced food regimen and gaining weight. Although he remains insulin-dependent (16 U/d), he is metabolically stable (HbA 1 c 5.9%). The fasting C-peptide level is 0.68 ng/mL. The peak value of C-peptide in response to oGTT was 0.92 ng/mL and to GS 0.89 ng/mL. At this time Ca19-9 and CEA are increased to 35.3 U/mL and 19.2 ng/mL, respectively. The patient died 2.5 years after operation owing to tumor recurrence. There was no evidence for liver metastases. We postulate that histologic evaluation (R 0-resection) and detection of K- ras mutations may be useful techniques. However, islet auto-Tx after EP for adenocarcinoma should only be regarded for rescue therapy. Studies on strategies to exclude possible contamination of islet tissue with carcinoma cells are critically important.

Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.

Patients with permanent neonatal diabetes usually present within the first three months of life and require insulin treatment. In most, the cause is unknown. Because ATP-sensitive potassium (K(ATP)) channels mediate glucose-stimulated insulin secretion from the pancreatic beta cells, we hypothesized that activating mutations in the gene encoding the Kir6.2 subunit of this channel (KCNJ11) cause neonatal diabetes. We sequenced the KCNJ11 gene in 29 patients with permanent neonatal diabetes. The insulin secretory response to intravenous glucagon, glucose, and the sulfonylurea tolbutamide was assessed in patients who had mutations in the gene. Six novel, heterozygous missense mutations were identified in 10 of the 29 patients. In two patients the diabetes was familial, and in eight it arose from a spontaneous mutation. Their neonatal diabetes was characterized by ketoacidosis or marked hyperglycemia and was treated with insulin. Patients did not secrete insulin in response to glucose or glucagon but did secrete insulin in response to tolbutamide. Four of the patients also had severe developmental delay and muscle weakness; three of them also had epilepsy and mild dysmorphic features. When the most common mutation in Kir6.2 was coexpressed with sulfonylurea receptor 1 in Xenopus laevis oocytes, the ability of ATP to block mutant K(ATP) channels was greatly reduced. Heterozygous activating mutations in the gene encoding Kir6.2 cause permanent neonatal diabetes and may also be associated with developmental delay, muscle weakness, and epilepsy. Identification of the genetic cause of permanent neonatal diabetes may facilitate the treatment of this disease with sulfonylureas.

The Case for Intravenous Arginine Stimulation In Lieu of Mixed-Meal Tolerance Tests as Outcome Measure for Intervention Studies in Recent-Onset Type 1 Diabetes

Residual β-cell function in patients with type 1 diabetes has been generally determined by C-peptide response to stimulation by a liquid mixed-meal tolerance test (MMTT) or intravenous glucagon (1). Early trials assessed benefits of therapy by frequency and duration of the clinical remission phase in which minimal or no exogenous insulin was needed to maintain euglycemia (reviewed in 2). What is now needed is the most sensitive, and not necessarily the most physiologic measure, so that any improvement in β-cell function during a clinical trial can be detected. Both the MMTT and the intravenous glucagon test have practical limitations. The MMTT takes 2–4 h to complete, and the stimulus is subject to variations in gastrointestinal absorption, while the intravenous glucagon test often invokes nausea. In contrast, the use of intravenous arginine to stimulate and measure β-cell secretion takes only a few minutes to perform, circumvents gastrointestinal variation, and is clinically well tolerated. In addition, responses to this nonglucose secretagogue have been demonstrated to persist after the diagnosis of diabetes at a time when responses to glucose are gone (3–6). Our goal was to determine whether arginine-stimulated C-peptide could be used in lieu of MMTT as an outcome measure for intervention studies in recent-onset type 1 diabetes. Institutional review board approval and informed consent were obtained before the study began. Nineteen subjects between 7–42 and 1–24 …

Increasing incidence of diabetes after gestational diabetes: a long-term follow-up in a Danish population.

To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes. Women with diet-treated GDM during 1978-1985 (old cohort, n = 241, also followed up around 1990) or 1987-1996 (new cohort, n = 512) were examined in 2000-2002. Women were classified by a 2-h, 75-g oral glucose tolerance test according to the World Health Organization criteria or an intravenous glucagon test supplemented by measurement of GAD antibodies. Historical data from index-pregnancy and anthropometrical measurements were collected. A total of 481 (63.9%) women were examined (median 9.8 years [interquartile range 6.4-17.2]) after index pregnancy. Diabetes and impaired glucose tolerance (IGT)/impaired fasting glucose were present in 40.0 and 27.0% of women, respectively. In the new cohort, 40.9% had diabetes compared with 18.3% in the old cohort at the 1990 follow-up (P < 0.0005). Prepregnancy BMI was significantly higher in the new compared with the old cohort (26.0 [22.5-30.8] vs. 22.9 kg/m2 [20.2-28.0], P < 0.0005). Among others, new-cohort membership, prepregnancy overweight (BMI > or = 25 kg/m2), and IGT postpartum were identified as independent predictors of diabetes by multiple logistic regression analyses. The incidence of diabetes among Danish women with previous diet-treated GDM was very high and had more than doubled over a 10-year period. This seems to be due to a substantial increase in BMI in women with GDM.

Clinical characterisation of severe hypoglycaemia--a prospective population-based study.

To determine the clinical characteristics of severe hypoglycaemia (SH) in a nonselected German population. SH was defined as an event requiring intravenous glucose or glucagon injection. The prospective population-based study screened sensitively for SH in a region with 200,000 inhabitants between 1997 and 2000. All 30,768 patients who presented to the regional central hospital emergency department, and 6,631 (85 %) of 7,804 patients attended by the emergency medical service in the region were given an initial blood glucose test to detect atypical hypoglycaemia. Altogether, 264 cases of SH were registered, which occurred either spontaneously (n = 14; 5 %), in subjects with type 1 (n = 92; 35 %) or type 2 diabetes (n = 148; 56 %), or in subjects with a non-classified form of diabetes (n = 10; 4 %). On the basis of the estimated local number of diabetic patients the annual rate of SH was 1.5 episodes per 100 patients in insulin-treated type 2 diabetics compared with a rate of 0.4 episodes per 100 patients for the overall group of type 2 diabetic patients. Nocturnal hypoglycaemia accounted for 44 % of episodes in patients with type 1 diabetes on intensified therapy but for only 25 % in patients with type 2 diabetes. 26 % of the hypoglycaemic individuals with type 1 diabetes had an impaired awareness of hypoglycaemia and thus recurrent hypoglycaemic episodes. Irrespective of the treatment, the most frequent contributing factors for SH in type 2 diabetic patients were advanced age (76 +/- 12 years), multimorbidity (3.6 +/- 2.6 concomitant diseases)--in particular renal impairment (54 % [80/148])--and polypharmacy (4 +/- 2.7 concomitant drugs). 34 % (50/148) of the subjects with type 2 diabetes lived in nursing homes or were cared for by a home nursing service. With standardised treatment zero mortality of SH in diabetic patients was achieved, only one non-diabetic died due to hepatic failure. In elderly, multimorbid patients approaching the insulin-deficient end of the spectrum of type 2 diabetes the risk of developing SH increases considerably, nearing that in patients with type 1 diabetes. In order to avoid SH in geriatric patients, the treatment targets should be defined critically, taking into account individual quality of life and life expectancy. Hypoglycaemia unawareness is a major risk factor for SH in type 1 diabetes.

Effectiveness of octreotide in a case of refractory sulfonylurea-induced hypoglycemia

The use of sulfonylurea medications in the treatment of type 2 diabetes mellitus is common. Patients who present to the Emergency Department after ingestion of excessive amounts of suflonylurea medications often have hypoglycemia refractory to dextrose administration. Standard care includes the administration of dextrose, glucagon, and diazoxide. Recently, the use of octreotide has been described as an alternative treatment in these patients. We present a case of a 20-year-old woman who ingested 900 mg of glyburide causing refractory hypoglycemia resistant to treatment with intravenous dextrose, glucagon, and diazoxide. Octreotide administration rapidly reversed hypoglycemia allowing patient stabilization and eventual discharge without any significant adverse events.

Does intravenous glucagon improve common bile duct visualisation during magnetic resonance cholangiopancreatography? Results in 42 patients

Introduction: Magnetic resonance cholangiopancreatography (MRCP) has been demonstrated as a reliable, non-invasive means of biliary tract imaging among patients with suspected choledocholithiasis. The aim of this study was to establish the impact of intravenous glucagon administration (IVGA) upon visualisation of the common bile duct (CBD) and ampulla of Vater during MRCP. Materials and methods: Forty-two consecutive, non-diabetic subjects with a working diagnosis of symptomatic choledocholithiasis were scanned, pre- and post-IVGA using the half-Fourier, single shot, turbo-spin-echo (HASTE) sequence. Maximum intensity projections (optimised for the extra-hepatic biliary tree and ampulla of Vater) were reviewed blindly by three consultant radiologists. The CBD images were graded (0–3) according to the length of duct seen. The ampullary images were graded according to whether to it was visualised clearly (1), or not (0). Results: Following IVGA the CBD was visualised at grade 3 (75–100% of length seen) in 14 additional patients compared with images prior to IVGA. Furthermore, ampullary visualisation was considered diagnostic in 18 additional patients post-IVGA. No glucagon-associated adverse effects were observed. Conclusion: These results demonstrate that IVGA improved visualisation of the CBD and ampulla of Vater during magnetic resonance cholangiopanctreatography. This may reduce the requirement for repeat investigation or recourse to invasive diagnostic procedures (e.g. endoscopic retrograde cholangiopancreatography (ERCP)).

Differential regional metabolism of glucagon in anesthetized pigs.

Glucagon metabolism under basal (endogenous) conditions and during intravenous glucagon infusion was studied in anesthetized pigs by use of midregion (M), COOH-terminal (C), and NH2-terminal (N)-RIAs. Arteriovenous concentration differences revealed a negative extraction of endogenous glucagon immunoreactivity across the portal bed (-35.4 +/- 11.0, -40.3 +/- 9.6, -35.6 +/- 16.9%, M-, C-, N-RIA, respectively), reflecting net secretion of pancreatic glucagon and intestinal glicentin and oxyntomodulin, but under exogenous conditions, a net extraction occurred (11.6 +/- 3.6 and 18.6 +/- 5.7%, C- and N-RIA, respectively). Hindlimb extraction of endogenous (17.4 +/- 3.7%, C-RIA) and exogenous (29.1 +/- 4.8 and 19.8 +/- 5.1%, C- and M-RIA) glucagon was detected, indicating M and C cleavage of the molecule. Renal extraction of glucagon was detected by all assays under endogenous (19.4 +/- 6.7, 33.9 +/- 7.1, 29.5 +/- 6.7%, M-, C-, N-RIA) and exogenous conditions (46.9 +/- 4.8, 46.4 +/- 6.0, 47.0 +/- 7.7%; M-, C-, N-RIA), indicating substantial elimination of the peptide. Hepatic glucagon extraction was undetectable under basal conditions and detected only by M-RIA (10.0 +/- 3.8%) during glucagon infusion, indicating limited midregional cleavage of the molecule. The plasma half-life determined by C- and N-RIAs (2.7 +/- 0.2 and 2.3 +/- 0.2 min) were similar, but both were shorter than when determined by M-RIA (3.2 +/- 0.2 min, P < 0.02). Metabolic clearance rates were similar regardless of assay (14.4 +/- 1.1, 13.6 +/- 1.7, 17.0 +/- 1.7 ml x kg-1 x min-1, M-, C-, N-RIA). Porcine plasma degraded glucagon, but this was not significantly affected by the dipeptidyl peptidase IV (DPP IV) inhibitor valine-pyrrolidide, and in anesthetized pigs, glucagon's metabolic stability was unchanged by DPP IV inhibition. We conclude that tissue-specific metabolism of glucagon occurs, with the kidney being the main site of removal and the liver playing little, if any, role. Furthermore, valine-pyrrolidide has no effect on glucagon stability, suggesting that DPP IV is unimportant in glucagon metabolism in vivo, in contrast to its significant role in the metabolism of the other proglucagon-derived peptides and glucose-dependent insulinotropic polypeptide.

An inadequate glycaemic response to glucagon is linked to insulin resistance in preterm infants?

Aims: To define clinical, metabolic, and hormonal characteristics of preterm infants relative to glucagon responsiveness. Methods: Two phase study of 78 preterm infants (25–36 weeks gestation) on regular four hourly...

Reproduction of Features of the Glucagonoma Syndrome with Continuous Intravenous Glucagon Infusion as Therapy for Tumor-Induced Hypoglycemia

To describe the adverse effects of continuous intravenous infusion of glucagon as therapy for tumor-induced hypoglycemia and to correlate these treatment-related effects with symptoms of endogenous hyper-glucagonemia. We reviewed three cases in which patients received continuous glucagon therapy for tumor-induced hypoglycemia and experienced adverse side effects to the treatment. We noted that these adverse events were consistent with changes that are described in the literature as symptoms of the glucagonoma syndrome. Continuous intravenous glucagon infusion has evolved as a reliable and efficacious modality for the treatment of tumor-induced hypoglycemia. We report the adverse events of venous thromboembolism, necrolytic migratory erythema, and angular cheilitis in conjunction with continuous intravenous glucagon treatment. These complications resemble symptoms that characterize the human model of hyperglucagonemia--the glucagonoma syndrome--which is associated with hyperglucagonemia and alpha-islet cell neoplasms of the pancreas. Symptoms that characterize the islet cell neoplasm-related glucagonoma syndrome may develop in patients receiving an infusion of exogenous glucagon. This observation lends support to the suggestion that glucagon may have a direct, causative role.

Intravenous glucagon: Does it optimize evaluation of the gastrointestinal tract on helical CT?

Forty outpatients were randomized into two groups of 20. Twenty patients received 1 mg of intravenous glucagon and the other 20 did not. Three radiologists evaluated the bowel using a qualitative score and mean scores for each bowel level were compared. A different radiologist measured the maximal diameter of bowel at seven levels. There were no significant differences in qualitative or quantitative data for the two groups. Intravenous glucagon is therefore not routinely recommended for helical CT of the abdomen.

Experience with intravenous glucagon infusions as a treatment for resistant neonatal hypoglycemia.

Based on limited anecdotal evidence, glucagon is used for the management of intractable neonatal hypoglycemia persisting in the face of high glucose administration rates. To evaluate the short-term response of blood glucose levels to an intravenous infusion of glucagon. A retrospective observational study in which all newborns who received glucagon infusions (usual dose, 0.5-1 mg/d) during a 5-year period were identified (N = 55). The common causes of hypoglycemia were perinatal stress, intrauterine growth restriction, prematurity, and maternal diabetes mellitus. Laboratory blood glucose measurements made between 24 hours before and 72 hours after the start of the glucagon infusion and the rates of glucose administration during the same period were analyzed. The effects of glucagon on sodium and platelet levels were also examined. University referral hospital. A statistically and clinically significant rise in blood glucose concentration, from a mean of 36.3 to 93.0 mg/dL (2.02-5.17 mmol/L), was observed within 4 hours of starting glucagon administration. The change was unrelated to the cause of the hypoglycemia. The frequency of hypoglycemic episodes was significantly reduced, and no further episodes of severe hypoglycemia (glucose level, <20 mg/dL [<1.1 mmol/L]) occurred. Five patients, 4 of whom were preterm newborns with intrauterine growth restriction, required additional glycemic treatment. Seventy-five percent of newborns were thrombocytopenic before starting glucagon infusion, and in 9 newborns platelet counts decreased following glucagon infusion. There was no hyponatremia attributable to glucagon. Glucagon infusions appear to be beneficial for problematic neonatal hypoglycemia of different causes.

CT colonography: colonic distention improved by dual positioning but not intravenous glucagon

The aim of this study was to determine whether intravenous (IV) glucagon and dual positioning administered prior to CT colonography enhances colonic distention. We assessed the effect of dual positioning and IV glucagon on colonic distention in 96 patients who underwent CT colonography examinations. The CT colonography was performed in both supine and prone positions. Seventy-four patients received glucagon (1 mg i.v.) immediately prior to CT scanning and 22 patients did not. The bowel was divided into ten segments and colonic distention was scored by two radiologists in the supine, prone, and combined supine/prone positions using a five-point scale: 1=collapsed; 2=poorly visualized; > or = 3=adequate distention; 4=entire segment visualized and well distended; 5=excellent distention). A combined segmental and overall supine/prone distention score was calculated based on the sum of the mean score for each position. There was no significant difference in the degree of colonic distention between patients who received glucagon and those who did not [supine/prone distention score (mean +/- SE): 3.63 +/- 0.2 vs 3.85 +/- 0.2; p=n.s.]. The degree of colonic distention was greater in the prone position in both the glucagon (3.87 +/- 0.2 vs 3.38 +/- 0.2; p<0.05) and non-glucagon groups (4.01 +/- 0.2 vs 3.69 +/- 0.2; p=N.S.) particularly in the proximal colon. There was almost perfect agreement between both radiologists in their scoring of colonic distention on a per-patient basis ( k=0.9; p<0.001). Of 1480 bowel segments, 1261 (85.2%) were adequately distended in the glucagon group compared with 370 of 440 bowel segments (84%) in the non-glucagon group ( p=n.s.) Colonic distention at CT colonography is improved by dual positioning but not by the administration of intravenous glucagon. While our results suggest that other smooth muscle relaxants, including butyl scopolamine, may only have a limited role in improving colonic distention in CT colonography, further studies are required.

Störungen der Glukosetoleranz bei Thalassaemia major

Fragestellung und Hintergrund. Bei Patienten mit Thalassaemia major fuhrt die Hamosiderose haufig zu Endokrinopathien. Wir untersuchten die Entwicklung von Glukosetoleranzstorungen und den Einfluss therapeutischer Masnahmen wie intensivierter Chelattherapie und Diat. Methode und Patienten. 60 Patienten mit Thalassaemia major im Alter von 4–36 Jahren, die regelmasige subkutane Deferoxamininfusionen sowie Bluttransfusionen erhielten, wurden hinsichtlich moglicher Endokrinopathien untersucht. Zur Untersuchung der Insulinsekretion dienten orale und i.-v.-Glukosebelastungen sowie der i.-v.-Glukagontest. Bei Patienten mit gestorter Glukosetoleranz wurde der Einfluss einer intensivierten (i. v.) Deferoxamintherapie und diatetischer Masnahmen auf Blutglukose- und Seruminsulinkonzentrationen untersucht. Ergebnisse. Glukosetoleranzstorungen zahlen ab dem 2. Lebensjahrzehnt zu den 4 haufigsten Hormonerkrankungen bei Patienten mit Thalassaemia major. Storungen der Glukosetoleranz gehen in einem Fruhstadium mit einer Hyperinsulinamie einher, spater entwickelt sich ein Insulinmangeldiabetes durch Erschopfung der β-Zell-Aktivitat. In der Fruhphase der Erkrankung fuhrten bei einigen Patienten eine Intensivierung der Deferoxamintherapie oder alleinige diatetische Behandlung zu einer Verbesserung der Glukosetoleranz. Schlussfolgerungen. Storungen der Glukosetoleranz lassen sich im Fruhstadium durch Diat und Intensivierung der Chelattherapie bessern. Die Manifestation eines Diabetes mellitus kann damit moglicherweise aufgehalten werden. Im fortgeschrittenen Stadium der Glukosetoleranzstorung liegt ein Insulinmangel vor, weshalb eine Insulinsubstitution notwendig wird.

The bronchodilator effect of intravenous glucagon in asthma exacerbation: A randomized, controlled trial

Study Objective: Glucagon is a rapid-acting smooth muscle relaxant with a short half-life. Previous studies suggested glucagon may have bronchodilator effects. We sought to determine whether intravenous glucagon produces clinically important immediate bronchodilation in emergency department patients with asthma exacerbation. Methods: We conducted a randomized, double-blind, placebo-controlled study at 2 university-affiliated community teaching hospital EDs (annual census 90,000). ED patients 18 to 50 years old with asthma exacerbation and peak expiratory flow rate (PEFR) less than 350 L/min were eligible. Exclusion criteria were need for intubation, chronic obstructive pulmonary disease, diabetes mellitus, insulinoma, pheochromocytoma, pregnancy, lactation, or current oral steroid treatment. Patients were randomly assigned to receive glucagon 0.03 mg/kg or an equivalent volume of saline solution intravenously. At 10 minutes, PEFR was measured and all patients began standardized albuterol therapy. Successful bronchodilation was a PEFR increase of 60 L/min at 10 minutes. Results: Success occurred in 2 (9.5%) of 21 glucagon-treated patients and 3 (12%) of 25 placebo-treated patients (95% confidence interval [CI] for difference of –2.5% [–20.4% to 15.4%]). Mean PEFR improvement for glucagon was 2 L/min versus 9 L/min for placebo (95% CI for difference of –7 L/min [–36 L/min to 23 L/min]). Conclusion: Glucagon alone provided no clinically important immediate bronchodilation in ED patients with asthma exacerbation. [Wilber ST, Wilson JE, Blanda M, Gerson LW, Meerbaum SO, Janas G. The bronchodilator effect of intravenous glucagon in asthma exacerbation: a randomized, controlled trial. Ann Emerg Med. November 2000;36:427-431.]

The bronchodilator effect of intravenous glucagon in asthma exacerbation: A randomized, controlled trial

The bronchodilator effect of intravenous glucagon in asthma exacerbation: A randomized, controlled trial

Does glucagon stimulation predict oral glucose tolerance in patients after simultaneous pancreas-kidney transplantation?

Exogenous glucagon rapidly stimulates insulin secretion. This test has been used to estimate insulin secretory capacity, which may predict oral glucose tolerance in patients after pancreas transplantation. In 32 pancreas-kidney transplant recipients, in 10 nondiabetic kidney transplant recipients, and in 9 healthy control subjects, a glucagon stimulation test (1 mg i.v.) and a 75-g oral glucose tolerance test were performed with determination of glucose, insulin, and C-peptide profiles. Of 16 pancreas transplant recipients with the lowest insulin responses after glucagon, 7 had an impaired oral glucose tolerance, in contrast to 1 of 16 with high insulin responses (P=0.037). A low insulin response after glucagon was associated with significantly lower 120-min glucose concentrations (P=0.043) and a lower integrated incremental insulin response after oral glucose (P=0.006). In pancreas-kidney transplant recipients, a low insulin response after intravenous glucagon predicts a reduced insulin response after oral glucose and an impaired oral glucose tolerance. This simple test may be helpful in the follow-up of pancreas transplant recipients.