***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 Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn ( NPH ) insulin in r and omized controlled trials . Evidence of severe hypoglycemic risk with insulin detemir , insulin glargine , or NPH insulin is presented from a nationwide retrospective data base study . Research design and methods Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin , insulin glargine , or insulin detemir in Finl and between 2000 and 2009 were analyzed . Incidence rates with 95 % confidence intervals ( CIs ) were calculated using Poisson regression . Hazard ratios were estimated using Cox 's regression with adjustments for relevant background variables . Results The adjusted risk of hospital/ secondary healthcare visits due to the first severe hypoglycemic event was 21.7 % ( 95 % CI 9.6–32.1 % , p < 0.001 ) lower for insulin detemir and 9.9 % ( 95 % CI 1.5–17.6 % , p = 0.022 ) lower for insulin glargine versus NPH insulin . Risk of hypoglycemic coma recurrence was 36.3 % ( 95 % CI 8.9–55.5 % , p = 0.014 ) lower for detemir and 9.5 % but not significantly ( 95 % CI −10.2 to 25.7 % , p = 0.318 ) lower for glargine versus NPH insulin . Risk of all hypoglycemic coma events was 30.8 % ( 95 % CI 16.2–42.8 % , p-value < 0.001 ) lower for detemir and 15.6 % ( 95 % CI 5.1–25.0 % , p-value 0.005 ) lower for glargine versus NPH . Insulin detemir had a significantly lower risk for first ( 13.1 % lower [ p = 0.034 ] ) , recurrent ( 29.6 % lower [ p = 0.021 ] ) , and all ( 17.9 % lower [ p = 0.016 ] ) severe hypoglycemic events than insulin glargine . Conclusions There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice In this open study of clinical practice , 142 paediatric patients with type 1 diabetes mellitus ( > 1 year duration ) , stratified by age , received pr and ial insulin ( regular or lispro ) and either once daily insulin glargine ( GLAR ; n=74 ) , titrated to target fasting blood glucose ( FBG ) levels 4.4 - 7.8 mmol/l , or NPH/semilente insulin ( NPH insulin , administered once , twice or three times daily ; n=68 ) , titrated to target FBG 4.4 - 8.9 mmol/l . Both groups were treated for 20 + /- 10 months . HbA(1c ) significantly increased in GLAR ( 7.3 + /- 1.0 % to 7.6 + /- 1.1 % ; p = 0.003 ) and NPH/semilente insulin ( 7.7 + /- 1.6 % to 8.3 + /- 1.5 % ; p = 0.0001 ) treated patients . The incidence of symptomatic hypoglycaemia was comparable between GLAR versus NPH/semilente insulin at endpoint ( 2.19 vs. 1.94 episodes/week ) ; however , the overall incidence of severe hypoglycaemia was significantly lower with GLAR versus NPH/semilente insulin ( 0.14 vs. 0.73 events/patient-year ; p = 0.002 ) . The daily insulin dose was similar between the treatment groups ; however , perceived quality of life ( QoL ) was better with GLAR . GLAR is associated with equivalent glycaemic control , less severe hypoglycaemia and improved QoL compared with NPH/semilente insulin OBJECTIVE To define the relationship between HbA(1c ) and plasma glucose ( PG ) levels in patients with type 1 diabetes using data from the Diabetes Control and Complications Trial ( DCCT ) . RESEARCH DESIGN AND METHODS The DCCT was a multicenter , r and omized clinical trial design ed to compare intensive and conventional therapies and their relative effects on the development and progression of diabetic complications in patients with type 1 diabetes . Quarterly HbA(1c ) and corresponding seven-point  capillary blood glucose profiles ( premeal , postmeal , and bedtime ) obtained in the DCCT were analyzed to define the relationship between HbA(1c ) and PG . Only data from complete profiles with corresponding HbA(1c ) were used ( n = 26,056 ) . Of the 1,441 subjects who participated in the study , 2 were excluded due to missing data .  Mean plasma glucose ( MPG ) was estimated by multiplying capillary blood glucose by 1.11 . Linear regression analysis weighted by the number of observations per subject was used to correlate MPG and HbA(1c ) . RESULTS Linear regression analysis , using MPG and HbA(1c ) summarized by patient ( n = 1,439 ) , produced a relationship of MPG ( mmol/l ) = ( 1.98 . HbA(1c ) ) - 4.29 or MPG ( mg/dl ) = ( 35.6 . HbA(1c ) ) - 77.3 , r = 0.82 ) . Among individual time points , afternoon and evening PG ( postlunch , predinner , postdinner , and bedtime ) showed higher correlations with HbA(1c ) than the morning time points ( prebreakfast , postbreakfast , and prelunch ) . CONCLUSIONS We have defined the relationship between HbA(1c ) and PG as assessed in the DCCT . Knowing this relationship can help patients with diabetes and their healthcare providers set day-to-day targets for PG to achieve specific HbA(1c ) goals OBJECTIVE To determine the efficacy and safety of insulin glargine ( IG ) in children and adolescents with type 1 diabetes . In a prospect i ve , 6-month study , 80 patients , aged 2 - 19 years , received IG once daily plus insulin regular or rapid analogue before meals . The data of body mass index , frequency of severe hypoglycaemia , daily mean blood glucose , fasting blood glucose , haemoglobin A1c and total daily insulin dosage before and after institution of glargine therapy were collected . RESULTS After 6 months , the average HbA1c level in the entire cohort dropped from 7.63+/-0.81 to 7.14+/-0.70 % ( p<0.001 ) . Fasting blood glucose decreased from 161+/-37 to 150+/-35 mg/dl ( p<0.05 ) in the total group . Severe hypoglycaemic episodes were reduced from 0.18 events per patient in the 6 months before IG therapy to 0.11 events per patient in the 6 months after IG therapy . The total daily insulin dose was reduced in the entire group from 0.90+/-0.32 to 0.83+/-0.29 u/kg/day ( p<0.05 ) . Body mass index ( BMI ) remained unchanged . In the 14 preschooler children , the HbA1c dropped from 7.54+/-0.60 to 6.96+/-0.57 % ( p<0.05 ) . CONCLUSIONS Insulin glargine is an efficacious treatment to improve metabolic control in children and adolescents with type 1 diabetes . It also improved the metabolic control in preschool-age children , without increasing the number of hypoglycaemic events BACKGROUND The goal of new therapies introduced for type 1 diabetes should be to decrease hypoglycemic episodes while improving glycemic control . METHODS A data base was used to computer match the baseline A1C values in 196 subjects with type 1 diabetes receiving multiple daily injections ( MDI ) consisting of four or more injections per day . There were 98 patients transferred from NPH to insulin glargine  ( Lantus , Aventis Pharmaceuticals , Bridgewater , NJ ) , and 98 patients remained on NPH throughout the study . The gender distribution and mean age ( approximately 32 years ) , duration of diabetes ( approximately 16 years ) , and duration of treatment ( approximately 13 months ) were not significantly different between the groups . The majority of patients were well controlled ( > 50 % in both groups had an A1C < 7 % ) . RESULTS The mean A1c values were not significantly different in the groups at baseline or at follow-up . Severe hypoglycemic episodes per patient per year were significantly lower in the glargine group compared with the NPH group ( 0.5 vs. 1.2 , respectively ; P = 0.04 ) . The mean end-of- study total ( P = 0.03 ) and long-acting ( P = 0.0001 ) doses were significantly reduced from baseline in the group that switched to glargine , but not in the group that remained on NPH , with no change in the short-acting dose in either group . The weight gain was significantly higher in the NPH group at the end of the study ( P = 0.004 ) with no significant change in the glargine group . CONCLUSIONS Transfer to glargine treatment from NPH in MDI regimens significantly reduces severe hypoglycemic episodes despite a decline in long-acting basal insulin without significant weight gain OBJECTIVE Insulin glargine offers sustained insulin delivery for 24 h. Change to glargine treatment consistently results in lower fasting glucose and fewer hypoglycemic episodes in children with type 1 diabetes compared to continuation of NPH , although glargine has not been shown to improve HbA1c in r and omized trials . Studies comparing glargine and NPH in multiple injection therapy in children treated from diagnosis of type 1 diabetes are lacking . METHODS HbA1c and insulin requirement were compared in a retrospective study of children ( 7 - 17 yr of age ) with type 1 diabetes treated from diagnosis with basal insulin glargine ( n = 49 ) or NPH ( n = 49 ) in a multiple injection therapy ( MIT ) regimen  with a rapid-acting insulin analogue . Patients were followed every third month for 1 yr . HbA1c , insulin dose , and weight data were retrieved . RESULTS HbA1c ( mean ± SD ) was lower at 3 - 5 months ( 5.5 ± 0.89 vs. 6.2 ± 0.89 % , p < 0.05 ) and 6 - 9 months ( 5.6 ± 1.14 vs. 6.6 ± 0.99 % ; p < 0.001 ) in glargine treated . After  
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Conclusion Given the high heterogeneity of the studies , the discrete value presented by the estimated effect on effectiveness and safety , potential conflicts of interest of the studies , and the appreciable higher cost of insulin glargine , there is still no support for recommending first-line therapy with analogs .