***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: OBJECTIVE Despite the demonstrated benefits of glycemic control , patient acceptance of basal/bolus insulin therapy for type 1 diabetes has been slow . We investigated whether a basal/bolus insulin regimen involving rapid-acting , dry powder , inhaled insulin could provide glycemic control comparable with a basal/bolus subcutaneous regimen . RESEARCH DESIGN AND METHODS Patients with type 1 diabetes ( ages 12 - 65 years ) received twice-daily subcutaneous NPH insulin and were r and omized to premeal inhaled insulin ( n = 163 ) or subcutaneous regular insulin ( n = 165 ) for 6 months . RESULTS Mean glycosylated hemoglobin ( A1C ) decreased comparably from baseline in the inhaled and subcutaneous insulin groups ( -0.3 and -0.1 % , respectively ; adjusted difference -0.16 % [ CI -0.34 to 0.01 ] ) , with a similar percentage of subjects achieving A1C < 7 % . Although 2-h postpr and ial glucose reductions were comparable between the groups , fasting plasma glucose levels declined more in the inhaled than in the subcutaneous insulin group ( adjusted difference -39.5 mg/dl [ CI -57.5 to -21.6 ] ) . Inhaled insulin was associated with a lower overall hypoglycemia rate but higher severe hypoglycemia rate . The overall hypoglycemia rate ( episodes/patient-month ) was 9.3 ( inhaled ) vs. 9.9 ( subcutaneous ) ( risk ratio [ RR ] 0.94 [ CI 0.91 - 0.97 ] ) , and the severe hypoglycemia rate ( episodes/100 patient-months ) was 6.5 vs. 3.3 ( RR 2.00 [ CI 1.28 - 3.12 ] ) . Increased insulin antibody serum binding without associated clinical manifestations occurred in the inhaled insulin group . Pulmonary function between the groups was comparable , except for a decline in carbon monoxide-diffusing capacity in the inhaled insulin group without any clinical correlates . CONCLUSIONS Inhaled insulin may provide an alternative for the management of type 1 diabetes as part of a basal/bolus strategy in patients who are unwilling or unable to use prepr and ial insulin injections OBJECTIVE This study , one of the first to address issues of pulmonary insulin delivery in smokers , compared pharmacokinetics of inhaled insulin delivered via the AERx insulin Diabetes Management System ( iDMS ) in nondiabetic cigarette smokers and nonsmokers . RESEARCH DESIGN AND METHODS In this r and omized two-period crossover efficacy and safety trial in 27 nondiabetic smokers and 16 nonsmokers ( 18 men/25 women , mean age 28 years , mean BMI 23.0 kg/m(2 ) ) , subjects received single doses of inhaled insulin ( 33.8 IU ) following overnight fasting on consecutive dosing days . On one dosing day , smokers smoked three cigarettes immediately before insulin administration ( " acute smoking " ) ; on the other dosing day , smokers had not smoked since midnight ( " nonacute smoking " ) . After inhalation , 6-h serum insulin and serum glucose profiles were determined . RESULTS Pharmacokinetic results for evaluable subjects were derived from serum insulin profiles . The amount of insulin absorbed during the first 6 h after dosing ( area under the exogenous serum insulin curve from 0 to 6 h [ AUC((0 - 6 h ) ) ] ) was significantly greater in smokers ( 63.2 vs. 40.0 mU l(-1 ) x h(-1 ) , P = 0.0017 ) ; peak concentration was both higher and earlier in the smokers ( maximal serum concentration of insulin [ C(max ) ] 42.0 vs. 13.9 mU/l , P < 0.0001 ; time to maximal serum concentration of insulin [ t(max ) ] 31.5 vs. 53.9 min , P = 0.0003 ) . The estimated intrasubject variability of AUC((0 - 6 h ) ) was 13.7 and 16.5 % for nonsmokers and smokers , respectively . No safety issues arose . CONCLUSIONS Absorption of inhaled insulin via the AERx iDMS was significantly greater in smokers , with a higher AUC((0 - 6 h ) ) and C(max ) and a shorter t(max ) . Intrasubject variability of AUC((0 - 6 h ) ) was low and similar in nonsmokers and smokers . These data prompt more extensive investigation of inhaled insulin in diabetic smokers BACKGROUND In patients with type 2 diabetes , published data suggest that glycemic control can be achieved as effectively with an inhaled insulin regimen ( prepr and ial inhaled intrapulmonary insulin plus a single bedtime Ultralente injection ) as with a conventional subcutaneous insulin regimen involving 2 to 3 injections per day . It is unknown whether inhalation delivery of insulin improves patient satisfaction . OBJECTIVE Our objective was to compare patient satisfaction between an inhaled insulin regimen and a subcutaneous insulin regimen . METHODS This was a 12-week r and omized , open-label , parallel-group , controlled trial in patients with type 2 diabetes . They were r and omized to receive either a subcutaneous insulin regimen ( split/mixed insulin with 2 to 3 injections daily ) or an inhaled insulin regimen ( inhaled insulin before meals and a single Ultralente insulin injection at bedtime ) . Change in glycosylated hemoglobin ( HbA1c ) from baseline to week 12 was the study 's primary end point . At baseline and week 12 , patients completed a question naire ( Patient Satisfaction with Insulin Therapy Question naire ) covering attributes of patient satisfaction . Treatment regimens were compared on each item with the Wilcoxon rank sum test and on the overall score with a t test . RESULTS Fifty-one patients ( age range , 35 - 65 years ) participated in the study , 26 receiving inhaled insulin and 25 receiving subcutaneous insulin .  Forty-seven patients ( 22 inhaled insulin , 25 subcutaneous insulin ) completed the satisfaction question naire . The mean percent improvement in overall satisfaction with an inhaled insulin regimen ( 31 % ; 95 % CI , 14 - 50 ) was significantly greater ( P < 0.05 ) than that with a subcutaneous insulin regimen ( 13 % ; 95 % CI , 7 - 19 ) . Increases in overall satisfaction correlated with improvements in glycemic control ( r = 0.30 ; P < 0.05 ) . Both treatment regimens experienced a mean HbA1c reduction of approximately 0.7 % . Although patient satisfaction was the chief focus of this article , these results should be considered exploratory , as the trial was powered prospect ively for HbA1c values ( the primary end point ) and not for patient satisfaction . CONCLUSIONS Administration of an inhaled insulin regimen may offer the first practical , noninvasive alternative to insulin injections . In the patients with type 2 diabetes studied , an inhaled insulin regimen with the need for only 1 subcutaneous injection at bedtime appeared to offer more ease of use , comfort , and convenience , as well as greater overall satisfaction , than a subcutaneous insulin regimen of 2 to 3 injections daily Abnormalities of pulmonary function tests have been described in type 1 ( insulin-dependent ) diabetes mellitus ( IDDM ) . To better characterise such abnormalities and to verify whether these latter are associated with the presence of diabetic microvascular disease we compared 23 non-smoking patients who had IDDM with 24 non-smoking healthy control subjects strictly matched for sex , age , and body mass index . Compared with controls , diabetic patients had a reduced forced vital capacity ( FVC ) ( 87.5 + /- 13.1 % vs. 96.4 + /- 13.6 % of the predicted ; P = 0.03 ) and forced expiratory volume in 1 s ( FEV1 ) ( 90.5 + /- 17.7 % vs. 101.2 + /- 13.2 % of the predicted ; P = 0.02 ) . While within the group of patients the presence of retinopathy and autonomic neuropathy were not associated with modifications of pulmonary function tests , those with altered urinary albumin excretion rate ( AER > or = 20 micrograms/min ; range 21 - 589 ) ( n = 7 ) had a significantly lower pulmonary diffusion capacity ( DLCO ) than the 16 normoalbuminuric subjects ( 62.6 + /- 7.2 % vs. 88.7 + /- 20.1 % of the predicted ; P = 0.01 ) . Moreover , in the group of patients , DLCO was inversely related with AER ( r = -0.43 ; P = 0.04 ) . In conclusion , IDDM is characterised by reduced FVC and FEV1 , while a significant decrease in DLCO may be considered as selectively associated with renal disease OBJECTIVE The AERx insulin Diabetes Management System ( AERx iDMS ) ( Aradigm , Hayward , CA ) delivers an aerosol of liquid human insulin to the deep lung for systemic absorption . This study examined the effects on pulmonary function , pharmacokinetics , and pharmacodynamics of inhaled insulin in asthmatic and nonasthmatic subjects without diabetes . RESEARCH DESIGN AND METHODS A total of 28 healthy and 17 asthmatic ( forced expiratory volume during the first second [ FEV(1 ) ] 50 - 80 % of predicted value ) subjects were enrolled in a two-part , open-label trial . To assess  insulin pharmacokinetics and pharmacodynamics , a single inhalation dose of 1.57 mg ( 45 IU ) was given on each of the 2 dosing days in part 1 . A dose of 4.7 mg ( 135 IU ) of insulin was inhaled in part 2 to assess effects on pulmonary function . RESULTS Inhaled insulin showed area under the curve (AUC)((0 - 360 min ) ) values that were significantly greater for healthy subjects than for asthmatic subjects ( P = 0.013 ) , whereas no difference was observed for maximum concentration ( C(max ) ) in the two groups . A greater reduction of serum glucose as indicated by area over the curve (AOC)((0 - 360 min ) ) was observed in healthy subjects ( P = 0.007 ) . Asthmatic subjects had greater intrasubject variations in insulin AUC((0 - 360 min ) ) and C(max ) values than healthy subjects , but similar variations in glucose AOC((0 - 360 min ) ) . No significant changes in FEV(1 ) , forced vital capacity ( FVC ) , and FEV(1)/FVC were observed from pre- to postdose times , and there were no observed safety issues . CONCLUSIONS After inhaling insulin using the AERx iDMS , asthmatic subjects absorbed less insulin than healthy subjects , result ing in less reduction of serum glucose . No effects on airway reactivity were observed . Diabetic patients with asthma may need to inhale more insulin than patients with normal respiratory function in order to achieve similar glycemic control OBJECTIVE Glycemic control using inhaled , dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes , which was previously managed with at least two daily insulin injections . RESEARCH DESIGN AND METHODS Patients were r and omized to 6 months ' treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente ( n = 149 ) or at least two daily injections of subcutaneous insulin ( mixed regular/NPH insulin ;  n = 150 ) . The primary efficacy end point was the change in HbA1c from baseline to the end of study . RESULTS HbA1c decreased similarly in the inhaled ( -0.7 % ) and subcutaneous ( -0.6 % ) insulin groups ( adjusted treatment group difference : -0.07 % , 95 % CI -0.32 to 0.17 ) . HbA1c < 7.0 % was achieved in more patients receiving inhaled ( 46.9 % ) than subcutaneous ( 31.7 % ) insulin ( odds ratio 2.27 , 95 % CI 1.24 - 4.14 ) . Overall hypoglycemia ( events per subject-month ) was slightly lower in the inhaled ( 1.4 events ) than in the subcutaneous ( 1.6 events ) insulin group ( risk ratio 0.89 , 95 % CI 0.82 - 0.97 ) , with no difference in severe events . Other adverse events , with the exception of increased cough in the inhaled insulin group , were similar . No difference in pulmonary function testing was seen . Further studies are underway to assess tolerability in the longer term . Insulin antibody binding increased more in the inhaled insulin group . Treatment satisfaction was greater in the 
    Output:
    
Patients preferred inhaled insulin over subcutaneous insulin .
Severe hypoglycemia was more likely with inhaled insulin than with oral agents .
Inhaled insulin caused mild to moderate nonprogressive dry cough and mild decreases in pulmonary function in some patients .