***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Biosynthetic glucagon ( GL-G ) produced by recombinant DNA technology with transformed yeast strains is already available for clinical use . We studied the effects of 1 mg GL-G injection on plasma glucose level and hypoglycemic symptoms in 38 diabetic patients treated with insulin or oral hypoglycemic agents during spontaneous hypoglycemic episodes . In both intramuscularly and intravenously administered GL-G groups , plasma glucose significantly increased from 58.1 + /- 11.4 to 113.2 + /- 6.9 mg/dl ( i.m . , n = 17 , P < 0.01 ) and from 76.4 + /- 4.4 to 125.7 + /- 5.9 mg/dl ( i.v . , n = 15 , P < 0.01 ) , respectively 20 min after the administration and the symptoms due to hypoglycemia subsided promptly after the injection of GL-G in 27 cases . The hyperglycemic effect of intramuscularly injected GL-G was more potent and long-st and ing than when intravenously injected , particularly in insulin-dependent diabetic ( IDDM ) patients . Neither significant changes of antibody levels against yeast proteins nor serious adverse effects were observed after GL-G administration . Biosynthetic glucagon is safe and useful for the treatment of hypoglycemia developing in diabetic patients Abstract 1 mg . glucagon was given i.m . or i.v . to a hundred hypoglycaemic diabetics unable to take glucose by mouth . Within 15 minutes forty were either awake or sufficiently roused to take oral glucose ; only one of the remaining sixty responded to a second injection of glucagon given 15 minutes after the first . There was no difference between the effect of i.m . and i.v . glucagon . The fifty-nine glucagon-unresponsive patients were given 25 g. dextrose i.v . ; thirty-six were awake within 15 minutes and another four responded to a second injection of 25 g. The remaining nineteen were still unconscious despite an adequate level of glycaemia having been achieved ( mean 247 : range 179 - 350 mg . per 100 ml . ) . They were treated with i.v . mannitol , dextrose , and steroids OBJECTIVE : We sought to establish the frequency of receiving > 1 dose of epinephrine in children who present to the emergency department ( ED ) with food-related anaphylaxis . PATIENTS AND METHODS : We performed a medical chart review at Boston hospitals of all children presenting to the ED for food-related acute allergic reactions between January 1 , 2001 , and December 31 , 2006 . We focused on causative foods , clinical presentations , and emergency treatments . RESULTS : Through r and om sampling and appropriate weighting , the 605 review ed cases represented a study cohort of 1255 patients . These patients had a median age of 5.8 years ( 95 % confidence interval [ CI ] : 5.3–6.3 ) , and the cohort was 62 % male . A variety of foods provoked the allergic reactions , including peanuts ( 23 % ) , tree nuts ( 18 % ) , and milk ( 15 % ) . Approximately half ( 52 % [ 95 % CI : 48–57 ] ) of the children met diagnostic criteria for food-related anaphylaxis . Among those with anaphylaxis , 31 % received 1 dose and 3 % received > 1 dose of epinephrine before their arrival to the ED . In the ED , patients with anaphylaxis received antihistamines ( 59 % ) , corticosteroids ( 57 % ) , epinephrine ( 20 % ) . Over the course of their reaction , 44 % of patients with food-related anaphylaxis received epinephrine , and among this subset of patients , 12 % ( 95 % CI : 9–14 ) received > 1 dose . Risk factors for repeat epinephrine use included older age and transfer from an outside hospital . Most patients ( 88 % ) were discharged from the hospital . On ED discharge , 43 % were prescribed self-injectable epinephrine , and only 22 % were referred to an allergist . CONCLUSIONS : Among children with food-related anaphylaxis who received epinephrine , 12 % received a second dose . Results of this study support the recommendation that children at risk for food-related anaphylaxis carry 2 doses of epinephrine Hypoglycaemia remains a serious and much feared complication of insulin therapy . In this study , patients attending an accident and emergency department in hypoglycaemic coma were r and omized to treatment with either intravenous dextrose ( 25 g ) or intramuscular glucagon ( 1 mg ) , administered into the right thigh . Restoration of normal conscious level was slower after glucagon than dextrose ( 9.0 vs 3.0 min , P less than 0.01 ) , although the average duration of hypoglycaemic coma was 120 min . Two patients in the glucagon-treated group , who failed to show satisfactory recovery after 15 min , required additional treatment with intravenous dextrose . On question ing following recovery , all except two patients reported loss of awareness of the onset of hypoglycaemia Intramuscular glucagon is valuable in the treatment of severe hypoglycaemia outwith hospital and , although the slightly slower and less predictable recovery may appear to make it a less attractive option than intravenous dextrose in the accident and emergency department , this must be balanced against the advantages of ease of administration and a lower incidence of serious adverse effects OBJECTIVE Glucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia . However , high insulin concentration lowers the hyperglycemic effect of glucagon , and small doses of glucagon in this setting are ineffective . There are no studies clearly defining the relationship between insulin levels , subcutaneous glucagon , and blood glucose . RESEARCH DESIGN AND METHODS Using a euglycemic clamp technique in 11 subjects with type 1 diabetes , we examined endogenous glucose production ( EGP ) of glucagon ( 25 , 75 , 125 , and 175 μg ) at three insulin infusion rates ( 0.016 , 0.032 , and 0.05 units/kg/h ) in a r and omized , crossover study . Infused 6,6-dideuterated glucose was measured every 10 min , and EGP was determined using a vali date d glucoregulatory model . Area under the curve ( AUC ) for glucose production was the primary outcome , estimated over 60 min . RESULTS At low insulin levels , EGP rose proportionately with glucagon dose , from 5 ± 68 to 112 ± 152 mg/kg ( P = 0.038 linear trend ) , whereas at high levels , there was no increase in glucose output ( 19 ± 53 to 26 ± 38 mg/kg , P = NS ) . Peak glucagon serum levels and AUC correlated well with dose ( r2 = 0.63 , P < 0.001 ) , as did insulin levels with insulin infusion rates ( r2 = 0.59 , P < 0.001 ) . CONCLUSIONS EGP increases steeply with glucagon doses between 25 and 175 μg at lower insulin infusion rates . However , high insulin infusion rates prevent these doses of glucagon from significantly increasing glucose output and may reduce glucagon effectiveness in preventing hypoglycemia when used in the artificial pancreas BACKGROUND Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention .  We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes . METHODS We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes , using Cox proportional-hazards models with adjustment for covariates measured at baseline and after r and omization . RESULTS During a median follow-up period of 5 years , 231 patients ( 2.1 % ) had at least one severe hypoglycemic episode ; 150 had been assigned to intensive glucose control ( 2.7 % of the 5571 patients in that group ) , and 81 had been assigned to st and ard glucose control ( 1.5 % of the 5569 patients in that group ) . The median times from the onset of severe hypoglycemia to the first major macrovascular event , the first major microvascular event , and death were 1.56 years ( interquartile range , 0.84 to 2.41 ) , 0.99 years ( interquartile range , 0.40 to 2.17 ) , and 1.05 years ( interquartile range , 0.34 to 2.41 ) , respectively . During follow-up , severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events ( hazard ratio , 2.88 ; 95 % confidence interval [ CI ] , 2.01 to 4.12 ) , major microvascular events ( hazard ratio , 1.81 ; 95 % CI , 1.19 to 2.74 ) , death from a cardiovascular cause ( hazard ratio , 2.68 ; 95 % CI , 1.72 to 4.19 ) , and death from any cause ( hazard ratio , 2.69 ; 95 % CI , 1.97 to 3.67 ) ( P<0.001 for all comparisons ) . Similar associations were apparent for a range of nonvascular outcomes , including respiratory , digestive , and skin conditions ( P<0.01 for all comparisons ) . No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death . CONCLUSIONS Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes . It is possible that severe hypoglycemia contributes to adverse outcomes , but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events . ( Funded by Servier and the National Health and Medical Research Council of Australia ; Clinical Trials.gov number , NCT00145925 . ) Summary The main therapeutic indication for glucagon is the treatment of hypoglycaemia in insulin overdosed Type 1 ( insulin-dependent ) diabetic patients . We have previously shown that an intranasal spray of 7.5 mg glucagon with deoxycholic acid as surfactant was able to correct an i.v . insulin-induced hypoglycaemia in diabetic patients . However , bioavailability and stability needed to be improved before intranasal glucagon could be introduced into clinical practice . This has now been achieved with a freeze-dried mixture of glucagon ( 1 mg ) and glycocholic acid ( 1 mg ) as a surfactant . Kinetics and efficacy have been controlled by ( 1 ) comparing subcutaneous and intranasal glucagon in 12 healthy non-hypoglycaemic subjects ; ( 2 ) testing intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by an i.v . bolus of insulin  and ( 3 ) comparing subcutaneous and intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by adding extra subcutaneous regular insulin to their usual morning dosage . Our results show that 1 mg of intranasal glucagon is as effective as 1 mg of subcutaneous glucagon in terms of the rise in blood glucose . Differences in kinetics between the subcutaneous and the intranasal routes may be observed : intranasal glucagon initiates the blood glucose rise earlier than does the subcutaneous form but the effect of the latter is more sustained . Glycocholic acid appears to be a perfectly tolerated agent in acute conditions . The use of intranasal lyophylized glucagon , for the reversal of hypoglycaemia in Type 1 diabetes , seems to be a clinical ly relevant alternative to its parenteral equivalent and should now be ready to be introduced in the market To estimate the frequency and morbidity of insulin-induced hypoglycaemia , a retrospective survey was undertaken of the frequency of severe hypoglycaemia in 600 r and omly selected patients with insulin-treated diabetes who were attending a large diabetic outpatient clinic in a teaching hospital . The result ing morbidity ( hypoglycaemia-related injuries , convulsions , and road traffic accidents ) was ascertained in 302 patients . One hundred and seventy-five ( 29.2 % ) of the 600 patients reported a total of 964 episodes of severe hypoglycaemia in the preceding year , giving an overall frequency for the group of 1.60 episodes patient-1year-1 . The frequency of severe hypoglycaemia which was documented in 544 Type 1 ( ketosis prone ) diabetic patients was double that observed in a subgroup of 56 Type 2 diabetic patients who were being treated with insulin ( 1.70 vs 0.73 episodes patient-1year-1 ) . In the subset of 3 
    Output:
    
Conclusions These data indicate that ineffectiveness of glucagon is unfrequent , not different from dextrose ; in addition , intranasal and injected glucagon are similarly effective .
In the case of failure , a second dose can be administered