***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 
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    Input: BACKGROUND AND AIM While lispro insulin has been reported to lower postpr and ial blood glucose concentrations , less consistent effects have been shown for glycosylated hemoglobin ( HbA1c ) levels . Aim of this study was to determine whether pre-meal association of NPH , an intermediate-acting insulin , with lispro improves overall glycemic control in type 1 diabetic patients . METHODS AND RESULTS Eighty-five type 1 diabetic patients were studied in a multicenter r and omized comparative ( human regular vs lispro insulin ) crossover ( 3-month ) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary . The number of injections was kept constant : 42 % and 58 % of patients injected insulin 3 and 4 times per day , respectively . Fasting and prepr and ial blood glucose levels were similar , while postpr and ial levels improved after lispro compared to human regular insulin ( breakfast : 8.28 + /- 2.39 vs 9.28 + /- 2.72 mmol/l ; lunch : 8.33 + /- 2.67 vs 9.06 + /- 2.67 mmol/l , dinner : 8.06 + /- 2.72 vs 9.28 + /- 2.44 mmol/l , ANOVA : p = 0.003 ) . HbA1c also improved after lispro : 8.1 + /- 0.9 vs 8.3 + /- 0.8 % , p < 0.05 . The rate of hypoglycemia was similar . Patients showed better acceptance of lispro treatment ( p < 0.001 ) . CONCLUSIONS Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia . This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long Summary The objective of this study was to identify possible risk factors of severe hypoglycaemia ( SH ) in a prospect i ve population based study of adult Type I ( insulin-dependent ) diabetic patients . A representative sample of 684 patients ( 41 % women , mean ± SD age 36 ± 11 , diabetes duration 18 ± 11 years ) , living in the district of Northrhine ( 9.5 million inhabitants ) , Germany , were examined in their homes using a mobile ambulance . A comprehensive baseline assessment of possible predictors of SH included sociodemographic and disease related variables , hypoglycaemia awareness , diabetes management , and attitudes and behavioural aspects as expressed by the patients . After a mean of 19 ± 6 months 669 ( 98 % ) patients were interviewed about events of SH since the baseline examination . Using the multiple Cox proportional hazards model , five risk factors of SH were identified : SH during the preceding year [ hazard ratio ( HR ) 2.7 , 95 % confidence intervals ( CI ) 1.8–4.2 ] , any history of SH ( HR 1.9 , CI 1.1–3.4 ) , C-peptide negativity ( HR 4.0 , CI 1.2–12.7 ) , social status ( HR 0.8 for a difference of 5 units for a value range of 0–24 , CI 0.6–0.9 ) , and patients ' determination to reach normoglycaemia ( HR 0.7 for a difference of 1 unit for a value range of 1–6 , CI 0.5–0.9 ) , indicating that the lower the social status and the higher the patients ' determination to reach normoglycaemia , the higher the risk of SH . After eliminating the history of hypoglycaemia from the model , impaired hypoglycaemia awareness and patients ' inappropriate denial of SH as their particular problem became additional significant risk factors of SH . In conclusion , in this population based study of adult Type I diabetic patients  , C-peptide negativity , a previous event of SH , patients ' determination to reach normoglycaemia and social class were risk factors of SH . [ Diabetologia ( 1998 ) 41 : 1274–1282 Insulin lispro is an insulin analogue that has the advantages of being fast-acting , convenient , and less likely to lead to hypoglycaemic episodes . Previous studies have proven its value in treating both Type 1 and Type 2 diabetes  both alone and in combination with different treatment regimens.1,2 However , diabetes is heterogeneous and differs in etiology and clinical characteristics in different ethnic groups . Even with the same insulin treatment , different diets will produce different glycaemic profiles . Diet patterns differ between different ethnic groups . Traditional oriental foods are characterized by a higher proportion of carbohydrates and a lower proportion of fat compared to Caucasian diets . To date , there has been no study on the use of insulin lispro in Chinese diabetic patients . Whether the Chinese dietary pattern will affect the efficacy of  insulin lispro treatment remains unknown . Therefore , we conducted this trial to assess the efficacy of insulin lispro treatment in Chinese patients The short-acting insulin analogue lispro ( [ LYS(B28 ) , PRO(B29 ) ] is absorbed from the subcutis more rapidly than soluble insulin ( S ) . To compare the clinical effectiveness of lispro vs S , 11 Type 1 patients using continuous subcutaneous insulin infusion ( CSII ) therapy ( 6 F , 5 M , age 30 + /- 2.5 years , diabetes duration 14 + /- 1.0 years , BMI 24.0 + /- 0.8 kg m(-2 ) , HbA1c 6.5 + /- 0.2 % ) were studied in an open , r and omized , crossover study for 6 months ( 3 months lispro and 3 months S or vice versa ) . During lispro treatment mean fasting and 2 h postpr and ial blood glucose were lower compared to the S phase ( fasting 6.5 + /- 0.4 vs 7.5 + /- 0.4 mmol l(-1 ) ( NS ) , postpr and ial 6.8 + /- 0.3 vs 8.3 + /- 0.3 mmol l(-1 ) , p = 0.03 ) . In patients treated first with lispro  HbA1c levels improved from 6.3 + /- 0.2 % to 5.7 + /- 0.3 % ; On reversion to S HbA1c increased to 6.2 + /- 0.2 % . In the group treated first with S , HbA1c fell ( 6.7 + /- 0.4 % vs 6.5 + /- 0.3 % ) and then improved further to 6.3 + /- 0.3 % with lispro . None of these changes were significant . There was no significant difference with respect to hypoglycaemic or other adverse events . It can be concluded that lispro in CSII therapy is safe and may improve postpr and ial glucose excursions BACKGROUND Although insulin lispro ( insulin LP ) has been shown to improve postpr and ial blood glucose ( BG ) control and reduce hypoglycemic episodes in adult patients with type I diabetes , there appear to have been few clinical studies focusing on its use in adolescents . OBJECTIVE This study compared the effects of insulin LP with those of regular human insulin ( insulin R ) on postpr and ial BG control and hypoglycemia in adolescents with type diabetes . METHODS In this crossover , open-label study , adolescents between the ages of 9 and 18 years who had reached Tanner stage II puberty were r and omized to receive either insulin LP immediately before meals or insulin R 30 to 45 minutes before meals , in addition to daily intermediate-acting insulin . After 4 months , patients were switched to the alternate treatment sequence . Eight-point BG profiles , hypoglycemia rate , and glycosylated hemoglobin ( HbA1c ) were measured at baseline and end point . RESULTS Four hundred eighty-one adolescents participated in the study at 53 investigative sites in 15 countries ; 463 were r and omized to treatment ( 228 insulin LP , 235 insulin R ) , and 457 completed the study .  Insulin LP given before breakfast result ed in significantly lower mean ( + /-SD ) 2-hour postpr and ial BG levels compared with insulin R ( 9.7 + /- 4.0 mmol/L vs 10.6 + /- 4.3 mmol/L , respectively ; P < 0.001 ) . Insulin LP given before dinner result ed in significantly lower 2-hour postpr and ial BG levels compared with insulin R ( 8.6 + /- 3.5 mmol/L vs 9.3 + /- 3.7 mmol/L ; P = 0.003 ) . No differences were seen between treatments in 2-hour postpr and ial BG levels after the midday meal . Mean baseline HbA1c values were similar between sequence groups , and no between-group difference in HbA1c was observed at end point ( insulin LP , 8.69 % + /- 1.52 % ; insulin R , 8.70 % + /- 1.65 % ) . Treatment with insulin LP result ed in a significantly lower incidence of hypoglycemic episodes per patient per 30 days compared with insulin R ( 4.02 + /- 4.5 vs 4.37 + /- 4.5 , respectively ; P = 0.023 ) and significantly fewer hypoglycemic episodes between midnight and 6 AM ( 1.0 + /- 1.9 vs 1.7 + /- 2.6 ; P < 0.001 ) . CONCLUSIONS In adolescents with type 1 diabetes , insulin LP significantly improved postpr and ial glycemic control and reduced episodes of nocturnal hypoglycemia compared with insulin R. Insulin LP was well tolerated and effective as part of an intensified insulin regimen in this study population OBJECTIVE The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart ( BIAsp 30 ) with the equivalent premixed biphasic human insulin ( BHI 30 ) , administered twice daily , in patients with type 2 diabetes mellitus . METHODS In this r and omized , double-blind , crossover trial , 13 patients ( mean age , 64 years ; baseline mean glycosylated hemoglobin , 7.7 % ; mean body mass index , 28.1 kg/m2 ) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast . At the end of each 2-week treatment period , 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays . All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance . RESULTS Total daily insulin exposure was similar between treatment periods . Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17 % greater than that of BHI 30 after dinner and 44 % greater after breakfast ; both differences were statistically significant . The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner ( 18 % ) and breakfast ( 35 % ) . Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group ; differences were significant only after breakfast . The mean daily pr and ial glucose excursion was significantly lower for BIAsp 30 ( 16.2 mmol x h x L(-1 ) ) than BHI 30 ( 17.9 mmol x h x L(-1 ) ) . Postpr and ial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast , but were significantly greater after lunch . Mean 24-hour and nocturnal serum glucose concentrations were similar , and both insulins were associated with < or = 7 minor and no major hypoglycemic events . CONCLUSIONS Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postpr and ial glucose excursions . This effect may be of importance when improvement in postpr and ial glucose control is desired Lispro ( LP ) and regular human ( HR ) insulins were compared in Type 1 diabetic ( T1DM ) patients on either a Mediterranean diet or normal diet . Twelve T1DM patients were recruited and r and omized into two groups of 6 , groups A and B. They were treated in different sequences ( in 3-month intervals for 1 year ) . Group A : LP insulin and normal diet , LP insulin and Mediterranean diet , regular insulin and Mediterranean diet , regular insulin and normal diet . Group B : regular insulin and normal diet , regular insulin and Mediterranean diet , LP insulin and Mediterranean diet , LP insulin and normal diet . Each patient was treated with rapid acting insulin , either LP insulin or HR insulin , before each main meal and a dose of slow acting insulin at bedtime . Every 15 days the glycemic control , the incidence and frequency of hypoglycemic episodes , and any adverse events were evaluated . Every 3 months , h 
    Output:
    
REVIEW ERS ' CONCLUSIONS Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin .