human
***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: Please cite this paper as : Ijäs H , Vääräsmäki M , Morin‐Papunen L , Keravuo R , Ebeling T , Saarela T , Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes : a prospect i ve r and omised study . BJOG 2011;118:880–885 AIM To compare treatment with metformin alone , metformin plus insulin and insulin alone in women with gestational diabetes ( GDM ) . METHOD A total of 150 gestational diabetic patients who fulfilled the eligibility criteria were included in this prospect i ve r and omized control open labeled study . A risk factor based screening was done followed by a GCT and then local GTT criteria from antenatal clinics . They were initially divided into two groups with odd numbers assigned to metformin treatment and even numbers to insulin treatment . Metformin and /or insulin treatment was given and target blood sugar levels aim ed at FBS ≤ 100 mg/dl and postpr and ial levels ≤ 126 mg/dl . Supplemental insulin was added to metformin treatment group to maintain the glycemic targets if required . Patients were followed until delivery and maternal fetal outcomes and pharmacotherapeutic characteristics were recorded on a performa . RESULTS Less maternal weight gain was found in the metformin treated groups ( 9.8 ± 1.5 kg [ metformin alone ] vs. 9.8 ± 1.4 kg [ metformin plus insulin ] vs. 12.5 ± 1.1 kg [ insulin alone ] P < 0.000 ) . Preeclampsia was significantly less in metformin treated groups . There were no perinatal deaths in the study . Mean birth weight was significantly less in metformin treated groups ( 3.4 ± 0.4 kg vs. 3.3 ± 0.5 kg vs. 3.7 ± 0.5 kg P < 0.01 ) . Less neonatal morbidity was observed in metformin groups . 42.7 % of patients required supplemental insulin ( mean dose of 13.6 ± 2 units ) in the  metformin group . Mean gestational age at which insulin was added was 31.8 ± 5.9 weeks . CONCLUSION Metformin is an effective and cheap treatment option for women with gestational diabetes with or without supplemental insulin Summary Background Maternal obesity is associated with increased birthweight , and obesity and premature mortality in adult offspring . The mechanism by which maternal obesity leads to these outcomes is not well understood , but maternal hyperglycaemia and insulin resistance are both implicated . We aim ed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes . Methods We did this r and omised , double-blind , placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK . Pregnant women ( aged ≥16 years ) between 12 and 16 weeks ' gestation who had a BMI of 30 kg/m2 or more and normal glucose tolerance were r and omly assigned ( 1:1 ) , via a web-based computer-generated block r and omisation procedure ( block size of two to four ) , to receive oral metformin 500 mg ( increasing to a maximum of 2500 mg ) or matched placebo daily from between 12 and 16 weeks ' gestation until delivery of the baby . R and omisation was stratified by study site and BMI b and ( 30–39 vs ≥40 kg/m2 ) . Participants , caregivers , and study personnel were masked to treatment assignment . The primary outcome was Z score corresponding to the gestational age , parity , and sex-st and ardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation . We did analysis by modified intention to treat . This trial is registered , IS RCT N number 51279843 . Findings Between Feb 3 , 2011 , and Jan 16 , 2014 , inclusive , we r and omly assigned 449 women to either placebo ( n=223 ) or metformin ( n=226 ) , of whom 434 ( 97 % ) were included in the final modified intention-to-treat analysis . Mean birthweight at delivery was 3463 g ( SD 660 ) in the placebo group and 3462 g ( 548 ) in the metformin group . The estimated effect size of metformin on the primary outcome was non-significant ( adjusted mean difference −0·029 , 95 % CI −0·217 to 0·158 ; p=0·7597 ) . The difference in the number of women reporting the combined adverse outcome of miscarriage , termination of pregnancy , stillbirth , or neonatal death in the metformin group ( n=7 ) versus the placebo group ( n=2 ) was not significant ( odds ratio 3·60 , 95 % CI 0·74–17·50 ; p=0·11 ) . Interpretation Metformin has no significant effect on birthweight percentile in obese pregnant women . Further follow-up of babies born to mothers in the EMPOWaR study will identify longer-term outcomes of metformin in this population ; in the meantime , metformin should not be used to improve pregnancy outcomes in obese women without diabetes . Funding The Efficacy and Mechanism Evaluation ( EME ) Programme , a Medical Research Council and National Institute for Health Research partnership AIMS We compared metformin with insulin as treatment of gestational diabetes mellitus ( GDM ) . Furthermore , we aim ed to characterize  metformin-treated patients needing additional insulin to achieve prespecified glucose targets . METHODS We conducted a single centre r and omized controlled study with non-inferiority design comparing metformin and insulin in the treatment of 217 GDM patients having birth weight as primary outcome variable . RESULTS There were no significant differences in mean birth weight expressed in grams [ + 15 ( 90 % confidence interval ( CI ) : -121 to 89 ) ] or SD units [ + 0.04 ( 90 % CI : -0.27 to 0.18 ) ] between the metformin and insulin groups . There were no significant differences in neonatal or maternal data between the groups . Only 23 ( 20.9 % ) of the 110 patients in the metformin group needed additional insulin .  Compared with the patients on metformin only , those needing additional insulin  were older ( p = 0.04 ) , their oral glucose tolerance test had been performed earlier and diabetes therapy started earlier in gestation ( p = 0.01 and p = 0.004 , respectively ) . The risk for additional insulin was 4.6-fold in women with baseline serum fructosamine concentration above median compared with those below median . CONCLUSIONS Metformin is an effective alternative to insulin in the treatment of GDM patients . Serum fructosamine may help in predicting the adequacy of metformin treatment alone Background : Few studies have been done on the use of metformin in pregnancy and their results were not similar , therefore this research is performed to compare neonatal outcomes of metformin and insulin in the treatment of gestational diabetes . Methods : In this prospect i ve r and omized trial , 200 pregnant women within their 24th to 34th weeks of gestation with gestational diabetes , single fetus pregnancy , and in need of hyperglycemia treatment were entered and grouped as either metformin or insulin . Data related to maternal and neonatal outcomes were recorded and analyzed . Results : Considering data recorded of HbA1c at the beginning of pregnancy , pregnancy induced hypertension , preeclampsia , birth weight , dystocia , first and 5th min APGAR , neonatal sepsis , rout of delivery , liver function tests of neonate , hypoglycemia , anomaly , and still birth , there were no significant statistical differences between groups . The end pregnancy HbA1c , maternal weight gain during pregnancy , preterm labor , neonatal jaundice , respiratory distress and hospitalization of infants were higher in insulin group . Conclusions : Considering data from this study , metformin is efficient to control hyperglycemia in pregnancy . It is suggested performing more studies to evaluate long term side effects of metformin in pregnancy with higher sample size and longer follow-up of newborns OBJECTIVE Factors associated with increasing  maternal triglyceride concentrations in late pregnancy include gestational age , obesity , preeclampsia , and altered glucose metabolism . In a subgroup of women in the Metformin in Gestational Diabetes ( MiG ) trial , maternal plasma triglycerides increased more between enrollment ( 30 weeks ) and 36 weeks in those treated with metformin compared with insulin . The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women . RESEARCH DESIGN AND METHODS Of the 733 women r and omized to metformin or insulin in the MiG trial , 432 ( 219 metformin and 213 insulin ) had fasting plasma triglycerides measured at enrollment and at 36 weeks . Factors associated with maternal triglycerides were assessed using general linear modeling . RESULTS Mean plasma triglyceride concentrations were 2.43 ( 95 % CI 2.35–2.51 ) mmol/L at enrollment . Triglycerides were higher at 36 weeks in women r and omized to metformin ( 2.94 [ 2.80–3.08 ] mmol/L ; + 23.13 % [ 18.72–27.53 % ] ) than insulin ( 2.65 [ 2.54–2.77 ] mmol/L , P = 0.002 ; + 14.36 % [ 10.91–17.82 % ] , P = 0.002 ) . At 36 weeks , triglycerides were associated with HbA1c ( P = 0.03 ) , ethnicity ( P = 0.001 ) , and treatment allocation ( P = 0.005 ) . In insulin-treated women , 36-week triglycerides were associated with 36-week HbA1c ( P = 0.02 ) , and in metformin-treated women , they were related to ethnicity . CONCLUSIONS At 36 weeks , maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin . Whether there are ethnicity-related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study AIM The aim of the study is to compare the effects of metformin and insulin treatment for gestational diabetes mellitus ( GDM ) on vitamin B12 and homocysteine ( Hcy ) status . METHODS Women with GDM , who met criteria for insulin treatment , were r and omly assigned to metformin ( n = 89 ) or insulin ( n = 91 ) in the Adelaide cohort of the metformin in gestational diabetes ( MiG ) trial .  Fasting serum total vitamin B12 ( TB12 ) , holotranscobalamin ( HoloTC ) , a marker of functional B12 status and plasma Hcy concentrations were measured at 20 - 34 weeks ( at r and omization ) and 36 weeks gestation , then at 6 - 8 weeks postpartum . RESULTS Circulating TB12 , HoloTC and Hcy were similar in both treatment groups at each time point . Women who were taking dietary folate supplements  at r and omization had higher serum TB12 and HoloTC at r and omization than those not taking folate . Overall , serum TB12 fell more between r and omization and 36 weeks gestation in the metformin group than in the insulin group ( metformin : -19.7 ± 4.7 pmol/l , insulin : -6.4 ± 3.6 pmol/l , p = 0.004 ) . The decrease in serum TB12 during treatment was greater with increasing treatment duration in metformin-treated ( p < 0.001 ) , but not in insulin-treated women . CONCLUSIONS Total , but not bioavailable , vitamin B12 stores were depleted during pregnancy to a greater extent in metformin-treated  than in insulin-treated women with GDM , but neither analyte differed between groups at any stage . This adds further evidence supporting metformin as a safe alternative treatment to insulin in GDM . Further investigation is needed to evaluate whether women treated with metformin for longer periods in pregnancy require additional B12 or other supplementation The purpose of the study was to examine in vivo placental transfer of metformin , its association with neonatal outcome in  metformin-treated gestational diabetes ( GDM ) patients , and influence of metformin exposure on maternal glycemic control and weight gain . Two hundred and seventeen GDM patients were r and omized to metformin or insulin in Turku University Hospital , Finl and . Metformin concentrations were determined by mass spectrometry in maternal serum at 36 gestational weeks ( gw ) and at birth , and in umbilical cord blood . Main outcome measures were birth weight , gw at birth , umbilical artery pH and neonatal hypoglycemia , maternal weight gain , HbA1c and fructosamine concentration . Median umbilical cord/maternal serum metformin concentration ratio 
    Output:
    
agent
***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: Please cite this paper as : Ijäs H , Vääräsmäki M , Morin‐Papunen L , Keravuo R , Ebeling T , Saarela T , Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes : a prospect i ve r and omised study . BJOG 2011;118:880–885 AIM To compare treatment with metformin alone , metformin plus insulin and insulin alone in women with gestational diabetes ( GDM ) . METHOD A total of 150 gestational diabetic patients who fulfilled the eligibility criteria were included in this prospect i ve r and omized control open labeled study . A risk factor based screening was done followed by a GCT and then local GTT criteria from antenatal clinics . They were initially divided into two groups with odd numbers assigned to metformin treatment and even numbers to insulin treatment . Metformin and /or insulin treatment was given and target blood sugar levels aim ed at FBS ≤ 100 mg/dl and postpr and ial levels ≤ 126 mg/dl . Supplemental insulin was added to metformin treatment group to maintain the glycemic targets if required . Patients were followed until delivery and maternal fetal outcomes and pharmacotherapeutic characteristics were recorded on a performa . RESULTS Less maternal weight gain was found in the metformin treated groups ( 9.8 ± 1.5 kg [ metformin alone ] vs. 9.8 ± 1.4 kg [ metformin plus insulin ] vs. 12.5 ± 1.1 kg [ insulin alone ] P < 0.000 ) . Preeclampsia was significantly less in metformin treated groups . There were no perinatal deaths in the study . Mean birth weight was significantly less in metformin treated groups ( 3.4 ± 0.4 kg vs. 3.3 ± 0.5 kg vs. 3.7 ± 0.5 kg P < 0.01 ) . Less neonatal morbidity was observed in metformin groups . 42.7 % of patients required supplemental insulin ( mean dose of 13.6 ± 2 units ) in the  metformin group . Mean gestational age at which insulin was added was 31.8 ± 5.9 weeks . CONCLUSION Metformin is an effective and cheap treatment option for women with gestational diabetes with or without supplemental insulin Summary Background Maternal obesity is associated with increased birthweight , and obesity and premature mortality in adult offspring . The mechanism by which maternal obesity leads to these outcomes is not well understood , but maternal hyperglycaemia and insulin resistance are both implicated . We aim ed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes . Methods We did this r and omised , double-blind , placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK . Pregnant women ( aged ≥16 years ) between 12 and 16 weeks ' gestation who had a BMI of 30 kg/m2 or more and normal glucose tolerance were r and omly assigned ( 1:1 ) , via a web-based computer-generated block r and omisation procedure ( block size of two to four ) , to receive oral metformin 500 mg ( increasing to a maximum of 2500 mg ) or matched placebo daily from between 12 and 16 weeks ' gestation until delivery of the baby . R and omisation was stratified by study site and BMI b and ( 30–39 vs ≥40 kg/m2 ) . Participants , caregivers , and study personnel were masked to treatment assignment . The primary outcome was Z score corresponding to the gestational age , parity , and sex-st and ardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation . We did analysis by modified intention to treat . This trial is registered , IS RCT N number 51279843 . Findings Between Feb 3 , 2011 , and Jan 16 , 2014 , inclusive , we r and omly assigned 449 women to either placebo ( n=223 ) or metformin ( n=226 ) , of whom 434 ( 97 % ) were included in the final modified intention-to-treat analysis . Mean birthweight at delivery was 3463 g ( SD 660 ) in the placebo group and 3462 g ( 548 ) in the metformin group . The estimated effect size of metformin on the primary outcome was non-significant ( adjusted mean difference −0·029 , 95 % CI −0·217 to 0·158 ; p=0·7597 ) . The difference in the number of women reporting the combined adverse outcome of miscarriage , termination of pregnancy , stillbirth , or neonatal death in the metformin group ( n=7 ) versus the placebo group ( n=2 ) was not significant ( odds ratio 3·60 , 95 % CI 0·74–17·50 ; p=0·11 ) . Interpretation Metformin has no significant effect on birthweight percentile in obese pregnant women . Further follow-up of babies born to mothers in the EMPOWaR study will identify longer-term outcomes of metformin in this population ; in the meantime , metformin should not be used to improve pregnancy outcomes in obese women without diabetes . Funding The Efficacy and Mechanism Evaluation ( EME ) Programme , a Medical Research Council and National Institute for Health Research partnership AIMS We compared metformin with insulin as treatment of gestational diabetes mellitus ( GDM ) . Furthermore , we aim ed to characterize  metformin-treated patients needing additional insulin to achieve prespecified glucose targets . METHODS We conducted a single centre r and omized controlled study with non-inferiority design comparing metformin and insulin in the treatment of 217 GDM patients having birth weight as primary outcome variable . RESULTS There were no significant differences in mean birth weight expressed in grams [ + 15 ( 90 % confidence interval ( CI ) : -121 to 89 ) ] or SD units [ + 0.04 ( 90 % CI : -0.27 to 0.18 ) ] between the metformin and insulin groups . There were no significant differences in neonatal or maternal data between the groups . Only 23 ( 20.9 % ) of the 110 patients in the metformin group needed additional insulin .  Compared with the patients on metformin only , those needing additional insulin  were older ( p = 0.04 ) , their oral glucose tolerance test had been performed earlier and diabetes therapy started earlier in gestation ( p = 0.01 and p = 0.004 , respectively ) . The risk for additional insulin was 4.6-fold in women with baseline serum fructosamine concentration above median compared with those below median . CONCLUSIONS Metformin is an effective alternative to insulin in the treatment of GDM patients . Serum fructosamine may help in predicting the adequacy of metformin treatment alone Background : Few studies have been done on the use of metformin in pregnancy and their results were not similar , therefore this research is performed to compare neonatal outcomes of metformin and insulin in the treatment of gestational diabetes . Methods : In this prospect i ve r and omized trial , 200 pregnant women within their 24th to 34th weeks of gestation with gestational diabetes , single fetus pregnancy , and in need of hyperglycemia treatment were entered and grouped as either metformin or insulin . Data related to maternal and neonatal outcomes were recorded and analyzed . Results : Considering data recorded of HbA1c at the beginning of pregnancy , pregnancy induced hypertension , preeclampsia , birth weight , dystocia , first and 5th min APGAR , neonatal sepsis , rout of delivery , liver function tests of neonate , hypoglycemia , anomaly , and still birth , there were no significant statistical differences between groups . The end pregnancy HbA1c , maternal weight gain during pregnancy , preterm labor , neonatal jaundice , respiratory distress and hospitalization of infants were higher in insulin group . Conclusions : Considering data from this study , metformin is efficient to control hyperglycemia in pregnancy . It is suggested performing more studies to evaluate long term side effects of metformin in pregnancy with higher sample size and longer follow-up of newborns OBJECTIVE Factors associated with increasing  maternal triglyceride concentrations in late pregnancy include gestational age , obesity , preeclampsia , and altered glucose metabolism . In a subgroup of women in the Metformin in Gestational Diabetes ( MiG ) trial , maternal plasma triglycerides increased more between enrollment ( 30 weeks ) and 36 weeks in those treated with metformin compared with insulin . The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women . RESEARCH DESIGN AND METHODS Of the 733 women r and omized to metformin or insulin in the MiG trial , 432 ( 219 metformin and 213 insulin ) had fasting plasma triglycerides measured at enrollment and at 36 weeks . Factors associated with maternal triglycerides were assessed using general linear modeling . RESULTS Mean plasma triglyceride concentrations were 2.43 ( 95 % CI 2.35–2.51 ) mmol/L at enrollment . Triglycerides were higher at 36 weeks in women r and omized to metformin ( 2.94 [ 2.80–3.08 ] mmol/L ; + 23.13 % [ 18.72–27.53 % ] ) than insulin ( 2.65 [ 2.54–2.77 ] mmol/L , P = 0.002 ; + 14.36 % [ 10.91–17.82 % ] , P = 0.002 ) . At 36 weeks , triglycerides were associated with HbA1c ( P = 0.03 ) , ethnicity ( P = 0.001 ) , and treatment allocation ( P = 0.005 ) . In insulin-treated women , 36-week triglycerides were associated with 36-week HbA1c ( P = 0.02 ) , and in metformin-treated women , they were related to ethnicity . CONCLUSIONS At 36 weeks , maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin . Whether there are ethnicity-related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study AIM The aim of the study is to compare the effects of metformin and insulin treatment for gestational diabetes mellitus ( GDM ) on vitamin B12 and homocysteine ( Hcy ) status . METHODS Women with GDM , who met criteria for insulin treatment , were r and omly assigned to metformin ( n = 89 ) or insulin ( n = 91 ) in the Adelaide cohort of the metformin in gestational diabetes ( MiG ) trial .  Fasting serum total vitamin B12 ( TB12 ) , holotranscobalamin ( HoloTC ) , a marker of functional B12 status and plasma Hcy concentrations were measured at 20 - 34 weeks ( at r and omization ) and 36 weeks gestation , then at 6 - 8 weeks postpartum . RESULTS Circulating TB12 , HoloTC and Hcy were similar in both treatment groups at each time point . Women who were taking dietary folate supplements  at r and omization had higher serum TB12 and HoloTC at r and omization than those not taking folate . Overall , serum TB12 fell more between r and omization and 36 weeks gestation in the metformin group than in the insulin group ( metformin : -19.7 ± 4.7 pmol/l , insulin : -6.4 ± 3.6 pmol/l , p = 0.004 ) . The decrease in serum TB12 during treatment was greater with increasing treatment duration in metformin-treated ( p < 0.001 ) , but not in insulin-treated women . CONCLUSIONS Total , but not bioavailable , vitamin B12 stores were depleted during pregnancy to a greater extent in metformin-treated  than in insulin-treated women with GDM , but neither analyte differed between groups at any stage . This adds further evidence supporting metformin as a safe alternative treatment to insulin in GDM . Further investigation is needed to evaluate whether women treated with metformin for longer periods in pregnancy require additional B12 or other supplementation The purpose of the study was to examine in vivo placental transfer of metformin , its association with neonatal outcome in  metformin-treated gestational diabetes ( GDM ) patients , and influence of metformin exposure on maternal glycemic control and weight gain . Two hundred and seventeen GDM patients were r and omized to metformin or insulin in Turku University Hospital , Finl and . Metformin concentrations were determined by mass spectrometry in maternal serum at 36 gestational weeks ( gw ) and at birth , and in umbilical cord blood . Main outcome measures were birth weight , gw at birth , umbilical artery pH and neonatal hypoglycemia , maternal weight gain , HbA1c and fructosamine concentration . Median umbilical cord/maternal serum metformin concentration ratio 
    Output:
    