***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 To study the pharmacodynamic properties of the subcutaneously injected long-acting insulin analog HOE901 ( 30 microg/ml zinc ) in comparison with those of NPH insulin and placebo . RESEARCH DESIGN AND METHODS In this single-center double-blind euglycemic glucose clamp study , 15 healthy male volunteers ( aged 27 + /- 4 years , BMI 22.2 + /- 1.8 kg/m2 ) received single subcutaneous injections of 0.4 U/kg body wt of HOE901 , NPH insulin , or placebo on 3 study days in a r and omized order . The necessary glucose infusion rates ( GIRs ) to keep blood glucose concentrations constant at 5.0 mmol/l were determined over a 30-h period after administration . RESULTS The injection of HOE901 did not induce the pronounced peak in metabolic activity observed with NPH insulin ( GIRmax 5.3 + /- 1.1 vs. 7.7 + /- 1.3 mg x kg(-1 ) x min(-1 ) ) ( P < 0.05 ) ; after an initial rise , metabolic activity was rather constant over the study period . This lack of peak was confirmed by a lower glucose consumption in the first 4 h after injection ( area under the curve from 0 to 4 h [ AUC(0 - 4 h ) ] 1.02 + /- 0.34 vs. 1.48 + /- 0.34 g/kg ) ( P < 0.001 ) with HOE901 , as compared with NPH insulin . In this single-dose study , the metabolic effect measured over a period of 30 h was lower with HOE901 than with NPH insulin ( AUC(0 - 30 h ) 7.93 + /- 1.82 vs. 9.24 + /- 1.29 g/kg ) ( P < 0.05 ) . CONCLUSIONS This study shows that the soluble long-acting insulin analog HOE901 induces a smoother metabolic effect than NPH insulin , from which a better substitution of basal insulin requirements may follow OBJECTIVE Insulin detemir is a soluble long-acting basal insulin analog design ed to overcome the limitations of conventional basal insulin formulations . Accordingly , insulin detemir has been compared with NPH insulin with respect to glycemic control ( HbA1c , prebreakfast glucose levels and variability , and hypoglycemia ) and timing of administration . RESEARCH DESIGN AND METHODS People with type 1 diabetes ( n = 408 ) were r and omized in an open-label , parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin . Insulin detemir was administered twice daily using two different regimens , either before breakfast and at bedtime ( IDet(morn+bed ) ) or at a 12-h interval ( IDet(12h ) ) . NPH insulin was administered before breakfast and at bedtime . Mealtime insulin was given as the rapid-acting insulin analog insulin aspart . RESULTS With both insulin detemir groups , clinic fasting plasma glucose was lower than with NPH insulin ( IDet(12h ) vs. NPH , -1.5 mmol/l [ 95 % CI -2.51 to -0.48 ] , P = 0.004 ; IDet(morn+bed ) vs. NPH , -2.3 mmol/l ( -3.32 to -1.29 ) , P < 0.001 ) , as was self-measured prebreakfast plasma glucose ( P = 0.006 and P = 0.004 , respectively ) . The risk of minor hypoglycemia was lower in both insulin detemir groups ( 25 % , P = 0.046 ; 32 % , P = 0.002 ; respectively ) compared with NPH insulin in the last 12 weeks of treatment , this being mainly attributable to a 53 % reduction in nocturnal hypoglycemia in the IDet(morn+bed ) group ( P < 0.001 ) . Although HbA1c for each insulin detemir group was not different from the NPH group , HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group ( mean difference -0.18 % [ -0.34 to -0.02 ] , P = 0.027 ) . Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups ( both P < 0.001 ) . The  NPH  group gained weight during the study , but there was no change in weight in either of the insulin detemir groups ( IDet(12h ) vs. NPH , -0.8 kg [ -1.44 to -0.24 ] , P = 0.006 ; IDet(morn+bed ) vs. NPH , -0.6 kg [ -1.23 to -0.03 ] , P = 0.040 ) . CONCLUSIONS Overall glycemic control with insulin detemir was improved compared with NPH insulin . The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person 's needs Aims /hypothesisThe aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy , using either the soluble long-acting basal insulin analogue , insulin detemir , in combination with the rapid-acting analogue , insulin aspart , or NPH insulin in combination with mealtime regular human insulin . Methods In this 18-week , 1:1 r and omised , open-labelled , parallel trial , 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively . Results Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin ( HbA1c : 7.88 % vs 8.11 % ; mean difference : −0.22 % point [ 95 % CI : −0.34 to −0.10 ] ; p<0.001 ) . Self-measured 8-point plasma glucose profiles differed between the groups ( p<0.001 ) , with lower postpr and ial plasma glucose levels in the insulin detemir/insulin aspart group . Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( SD : 2.88 vs 3.12 mmol/l ; p<0.001 ) . Risk of overall and nocturnal hypoglycaemia ( 23.00–06.00 hours ) was , respectively , 21 % ( p=0.036 ) and 55 % ( p<0.001 ) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin  group . Body weight ( adjusted for baseline and change in HbA1c ) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( p<0.001 ) . Conclusions /interpretationBasal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin . The low variability and more physiological action profiles generated with these insulin analogues result ed in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase AIM To compare glycaemic control and symptomatic hypoglycaemia rates with glargine versus neutral protamine Hagedorn ( NPH ) in poorly controlled type 1 diabetes patients . METHODS Patients ( n = 125 ) received prepr and ial insulin lispro and either glargine ( n = 62 ) or NPH ( n = 63 ) at bedtime for 30 weeks in a multicentre , r and omized , single-blind ( a blinded investigator made titration decisions ) study . Basal insulin dosage was titrated to achieve fasting blood glucose ( FBG ) values < 5.5 mmol/L. RESULTS Baseline characteristics were similar for the two groups ( mean diabetes duration 17.5 + /- 10.1 years ) except mean glycated haemoglobin ( HbA(1c ) ) , which was lower in the glargine versus NPH group ( 9.2 + /- 1.1 % vs 9.7 + /- 1.3 % ; P < 0.02 ) . At end-point , mean HbA(1c ) was 8.3 versus 9.1 % for the glargine versus NPH groups . Adjusted least-squares mean ( LSM ) change from baseline was -1.04 versus -0.51 % , a significant treatment benefit of 0.53 % for HbA(1c ) in favour of glargine ( P < 0.01 ) . Mean baseline FBG were similar for the glargine and NPH groups ( 11.2 vs 11.4 mmol/L ) . The means for end-point FBG were 7.9 versus 9.0 mmol/L. Adjusted LSM change from baseline was -3.46 versus -2.34 mmol/L , with a significant difference of 1.12 mmol/L in favour of glargine ( P < 0.05 ) . There were similar total numbers of daytime mild , moderate or severe hypoglycaemia episodes in the two treatment arms . However , significantly fewer moderate or severe nocturnal hypoglycaemic episodes were observed in the glargine group ( P = 0.04 and P = 0.02 ) . CONCLUSION Glargine is superior to NPH for improving HbA(1c ) and FBG levels during intensive insulin therapy in patients with type 1 diabetes , and is associated with less severe nocturnal hypoglycaemia Abstract .The purpose of this study was to determine the feasibility of a flexible multiple daily insulin ( FMDI ) regimen in routine pediatric diabetes care by comparing HbA1c , body mass index ( BMI ) , and episodes of severe hypoglycemia ( SH ) before and after initiation of FMDI therapy .  Data from 44 patients ( 2–16 years old ) , on a conventional insulin ( CI ) regimen , were collected during quarterly diabetes clinic visits . These patients were transitioned from CI to FMDI regimen : pre-meal lispro ( bolus ) and once or twice daily Humulin Ultralente with or without bedtime Humulin NPH as the basal insulin . There was a significant improvement in HbA1c in prepubertal ( 9.3%±1.3 % vs. 8.0%±1.1 % , p<0.002 ) and pubertal subjects ( 9.2%±1.0 % vs. 8.2%±0.9 % , p<0.001 ) . Pubertal subgroup demonstrated an increase in BMI ( 21.3±3.1 vs. 22.7±3.2 kg/m2 , p<0.0001 ) after one year . The rate of SH was decreased in both prepubertal ( p<0.01 ) and pubertal ( p<0.05 ) groups of patients on FMDI therapy . The use of FMDI in a general pediatric diabetic population is a feasible therapeutic option for maintenance and possible improvement of glycemic control . It may effectively decrease the HbA1c , and reduce hypoglycemic episodes , without producing an abnormal increase in BMI OBJECTIVE To determine the safety and efficacy of the long-acting insulin analog , insulin glargine , as a component of basal bolus therapy in patients with type 1 diabetes . RESEARCH DESIGN AND METHODS Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro  were r and omized to receive insulin glargine ( HOE 901 ) , a long-acting basal insulin analog , once a day ( n = 310 ) or NPH human insulin ( n = 309 ) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH  insulin  patients maintained their prior schedule of administration once or twice a day , whereas insulin glargine patients received basal insulin once a day at bedtime . RESULTS Compared with all NPH insulin patients , insulin glargine patients had significant decreases in fasting blood glucose measured at home ( means + /- SEM , -42.0 + /- 4.7 vs. -12.4 + /- 4.7 mg/dl [ -2.33 + /- 0.26 vs. -0.69 + /- 0.26 mmol/l ] ; P = 0.0001 ) . These differences were evident early and persisted throughout the study More patients in the insulin glargine group ( 29.6 % ) than in the NPH group ( 16.8 % ) reached a target fasting blood glucose of 119 mg/dl ( < 6.6 mmol/l ) . However , there were no differences between the groups with respect to change in G 
    Output:
    
Weight gain was more prominent in the control group .
No difference was noted in the quantity or quality of severe adverse events or deaths .
AUTHORS ' CONCLUSIONS Long acting insulin preparations seem to exert a beneficial effect on nocturnal glucose levels .
Their effect on the overall diabetes control is clinical ly unremarkable .