***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: 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 OBJECTIVE Insulin administered by jet injectors is dispensed over a larger subcutaneous area than insulin injected with a syringe , which may facilitate a more rapid absorption . This study compared the pharmacologic profile of administration of insulin aspart by jet injection to that by conventional insulin pen . RESEARCH DESIGN AND METHODS Euglycemic glucose clamp tests were performed in 18 healthy volunteers after subcutaneous administration of 0.2 units/kg body wt of aspart , either administered by jet injection or by conventional pen , using a r and omized , double-blind , double-dummy , cross over study design . Pharmacodynamic and pharmacokinetic profiles were derived from the glucose infusion rate ( GIR ) needed to maintain euglycemia and from plasma insulin levels , respectively . RESULTS The time to maximal GIR was significantly shorter when insulin was injected with the jet injector compared with conventional pen administration ( 51 ± 3 vs. 105 ± 11 min , P < 0.0001 ) . The time to peak insulin concentration was similarly reduced ( 31 ± 3 vs. 64 ± 6 min , P < 0.0001 ) and peak insulin concentrations were increased ( 108 ± 13 vs. 79 ± 7 mU/L , P = 0.01 ) when insulin was injected by jet injection compared with conventional pen injection . Jet injector insulin administration reduced the time to 50 % glucose disposal by ∼40 min ( P < 0.0001 ) . There were no differences in maximal GIR , total insulin absorption , or total insulin action between the two devices . CONCLUSIONS Administration of insulin aspart by jet injection  enhances insulin absorption and reduces the duration of glucose-lowering action . This profile resembles more closely the pattern of endogenous insulin secretion and may help to achieve better meal insulin coverage and correction of postpr and ial glucose excursions OBJECTIVE To evaluate the progression of retinopathy during pregnancy and postpartum in ( insulin-dependent ) women with type 1 diabetes treated with insulin lispro or with regular human insulin .  RESEARCH DESIGN AND METHODS A prospect i ve open study of 69 pregnant women with diabetes was performed . A total of 36 of the women were treated with insulin lispro ( lispro group ) and 33 were treated with conventional short-acting human insulin ( regular insulin group ) . The retinopathy level was estimated by color fundus photography every trimester and postpartum . Glycemic control during pregnancy , hypoglycemia ( blood glucose level <3 mmol/l ) in 24-h glucose profile , blood pressure , and proteinuria were registered . RESULTS HbA(1c ) values were similar at baseline in the first trimester but thereafter were lower in the lispro group than in the regular insulin group throughout pregnancy ( P = 0.022 , repeated- measures ANOVA ) . The number of hypoglycemic episodes did not differ between the treatment groups . In multivariable logistic regression analysis with retinopathy severity ( Diabetes Control and Complications Trial level ) in the third trimester as the dependent variable , only nulliparity qualified as a predictor in the model [ Exp(B ) = 4.0 , 95 % CI 1.1 - 13.7 , P = 0.030 ] . Factors such as duration of diabetes , type of insulin used , mean HbA(1c ) level throughout pregnancy , blood pressure ( systolic or diastolic ) , preeclampsia in the current pregnancy , smoking , or prepregnancy planning did not explain the retinopathy progression . CONCLUSIONS Insulin lispro improves glycemic control during diabetic pregnancy compared with regular insulin with no adverse impact on progression of diabetic retinopathy INTRODUCTION Insulin glulisine ( glulisine ) was evaluated versus regular human insulin ( RHI ) in Type 2 diabetes ( T2DM ) patients . METHODS Patients previously on > 6 months ' continuous insulin treatment aged > or=18 years in a r and omized , multinational , controlled , open-label , parallel group , 26-week study received twice-daily NPH insulin and either glulisine ( 0 - 15 min before breakfast and dinner ; n=448 ) or RHI ( 30 - 45 min before breakfast and dinner ; n=442 ) at least twice daily . RESULTS Mean baseline characteristics were similar between groups . There were no differences in baseline to endpoint HbA(1c ) reductions ( glulisine : -0.32 % ; RHI : -0.35 % ; p=0.5726 ) , and the non-inferiority of glulisine versus RHI was demonstrated ( difference in adjusted mean change 0.03 % ; 95 % CI : -0.07 , 0.13 ) . Postpr and ially , glulisine  lowered plasma glucose significantly more versus RHI at 2h ( 14.14 mmol/L versus 15.28 mmol/L ; p=0.0025 ) and excursions at 1h ( 3.99 versus 4.59 ; p=0.0151 ) and 2h ( 4.87 versus 6.03 ; p=0.0002 ) . No between-group differences occurred in the frequencies and monthly rates of all symptomatic hypoglycaemia ; nocturnal hypoglycaemia from Month 4 to treatment end was less frequent with glulisine versus RHI ( 9.1 % versus 14.5 % ; p=0.029 ) . CONCLUSION Glulisine was non-inferior to RHI in reducing HbA(1c ) in T2DM . Glulisine demonstrated superior postpr and ial glucose control and was associated with fewer nocturnal hypoglycaemic episodes , indicating clinical benefits Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Today , insulin analogs are used in millions of diabetic patients .  Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time-course of the effect . Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin . However , these changes can also modify the molecular and biological effects of the analogs . The rapid-acting insulin analogs , lispro , aspart , and glulisine , have a rapid onset and shorter duration of action . The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile . Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation . A major question is whether analogs have an increased mitogenic activity in respect to insulin . These lig and s can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor , stimulation of the IGF-1 receptor ( IGF-1R ) , prevalent activation of the extracellular-signaling-regulated kinase ( ERK ) rather than the protein kinase B ( PKB/AKT ) intracellular post-receptor pathways . Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin . In contrast , long-acting analogs behave differently . Although not all data are homogeneous , both glargine and detemir have been found to have a decreased binding to receptors for insulin but an increased binding to IGF-1R , a prevalent activation of the ERK pathway , and an increased mitogenic effect in respect to insulin . Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs ( specifically glargine ) may increase the relative risk for cancer . Results are controversial and method ologically weak . Therefore prospect i ve clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin analogs 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 
    Output:
    
We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life .
However , there were few results only based on subgroups of the trial population s. None of the trials reported substantial effects regarding weight gain or any other adverse events .
Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes .