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: Screening for glucose intolerance during pregnancy provides an opportunity to offer management to those women diagnosed with gestational diabetes mellitus . However , there is a need to diagnose gestational diabetes early to minimize exposure of the developing fetus to suboptimal conditions and prevent perinatal complications and their sequelae . The purpose of this study was to identify potential biomarkers for impending gestational diabetes that appear in the plasma before impaired glucose tolerance . Pregnant women were prospect ively recruited to the study and blood was collected at the first antenatal visit and at the time of routine oral glucose tolerance test . Women diagnosed with gestational diabetes were matched with an equal number of normal pregnant ( control ) women . Biomarkers under investigation included endocrine and metabolic hormones , cytokines and chemokines , and surrogate markers of oxidative stress . Compared to controls , women with gestational diabetes exhibited elevated plasma insulin and reduced plasma adiponectin concentrations at 28 weeks gestation . Significant differences in insulin and adiponectin concentrations were also observed in plasma at 11 weeks gestation . Bivariate logistic regression analysis showed that both insulin and adiponectin are associated with subsequent development of gestational diabetes . Plasma insulin and adiponectin concentrations , when measured at 11 weeks , may be predictive of impending gestational diabetes . Further studies are warranted to determine the reliability of these biomarkers OBJECTIVE : Emerging evidence suggests that leptin , an adipocyte-derived hormone , may have independent direct effects on both insulin secretion and action , in addition to its well documented effects on appetite and energy expenditure . Some , but not all , previously published studies suggest that maternal leptin concentrations may be increased in pregnancies complicated by gestational diabetes mellitus ( GDM ) . We examined the association between plasma leptin concentration and GDM risk . METHODS : Women were recruited before 16 weeks of gestation and were followed up until delivery .  Maternal plasma leptin concentrations  ( collected at 13 weeks of gestation ) were measured by using immunoassay . We used generalized linear models to estimate relative risks and 95 % confidence intervals . RESULTS : GDM developed in 5.7 % of the cohort ( 47 of 823 ) . Elevated leptin concentrations were positively associated with GDM risk ( P for trend < .001 ) . After adjusting for maternal prepregnancy adiposity and other confounders , women with leptin concentrations of 31.0 ng/mL or higher experienced a 4.7-fold increased risk of GDM ( 95 % confidence interval 1.2 , 18.0 ) as compared with women who had concentrations of 14.3 ng/mL or lower . We noted a strong linear component of trend in risk of GDM with increasing maternal plasma leptin concentration . Each 10-ng/mL increase in the leptin concentration was associated with a 20 % increase in GDM risk ( relative risk 1.2 ; 95 % confidence interval 1.0 , 1.3 ) . CONCLUSIONS : Hyperleptinemia , independent of maternal adiposity , in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy . Additional larger prospect i ve cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy . LEVEL OF EVIDENCE : AIM To examine the prediction of gestational diabetes in obese women using routine clinical measures and measurement of biomarkers related to insulin resistance in the early second trimester . METHODS A total of 117 obese pregnant women participating in a pilot trial of a complex intervention of dietary advice and physical activity  were studied . Blood sample s were obtained at recruitment ( 15⁺⁰-17⁺⁶ weeks ' gestation ) and demographic , clinical history and anthropometric measures recorded . The biomarkers analysed were plasma lipids ( HDL cholesterol , LDL cholesterol , triglycerides ) , high-sensitivity C-reactive protein , alanine transaminase , aspartate transaminase , ferritin , fructosamine , insulin , adiponectin , tissue plasminogen activator , interleukin-6 , visfatin and leptin . Univariate and logistic regression analyses were performed to determine independent predictors and area under the receiver-operating curve was calculated for the model . RESULTS Of the 106 participants included in the analysis , 29 ( 27.4 % ) developed gestational diabetes . Participants with gestational diabetes were older ( P = 0.002 ) , more often of parity ≥ 2 , had higher systolic ( P = 0.02 ) and diastolic blood pressure ( P = 0.02 ) and were more likely to be black ( P = 0.009 ) . Amongst the blood biomarkers measured , plasma adiponectin alone remained independently associated with gestational diabetes in adjusted models ( P = 0.002 ) . The area under the receiver-operating curve for clinical factors alone ( 0.760 ) increased significantly ( area under the curve 0.834 , chi-square statistic ( 1 ) = 4.00 , P = 0.046 ) with the addition of adiponectin . CONCLUSIONS A combination of routinely measured clinical factors and adiponectin measured in the early second trimester in obese women may provide a useful approach to the prediction of gestational diabetes . Validation in a large prospect i ve study is required to determine the usefulness of this algorithm in clinical practice Nuala Sheehan and colleagues describe how Mendelian r and omization provides an alternative way of dealing with the problems of observational studies , especially confounding OBJECTIVE To develop a model for the prediction of gestational diabetes mellitus ( GDM ) from maternal characteristics and biochemical markers at 11 to 13 weeks ' gestation . METHODS A prospect i ve screening study on early prediction of pregnancy complications ( n = 11 , 464 ) , including 297 ( 2.6 % ) cases of GDM was used to create the predictive model of GDM based on maternal characteristics .  Maternal serum concentrations of adiponectin , follistatin-like-3 ( FSTL3 ) and sex hormone-binding globulin ( SHBG ) were measured in a case-control study of 80 women who developed GDM and 300 controls . RESULTS In the screening study , maternal age , body mass index , racial origin , previous history of GDM and macrosomic neonate were significant independent predictors of future GDM . In the GDM group , compared to controls , the median multiple of the normal median adiponectin ( 0.66 ; IQR : 0.5 - 0.9 vs 1.02 ; IQR : 0.7 - 1.29 ) and SHBG ( 0.81 ; IQR : 0.6 - 1.04 vs 1.02 ; IQR : 0.8 - 1.2 ) was lower ( p < 0.05 ) , but FSTL3 was not significantly different . In screening for GDM by maternal characteristics , the detection rate was 61.6 % at a false-positive rate of 20 % and the detection increased to 74.1 % by the addition of adiponectin and SHBG . CONCLUSION First-trimester screening for GDM can be provided by a combination of maternal characteristics and biomarkers OBJECTIVE We prospect ively examined plasma levels of leptin and soluble leptin receptor ( sOB-R ) , as well as their interactions with other diabetes risk factors , in relation to type 2 diabetes to eluci date the complex relation between these two biomarkers and diabetes risk . RESEARCH DESIGN AND METHODS Of 32,826 Nurses ' Health Study participants who provided blood sample s during 1989–1990 , 1,054 incident case subjects of type 2 diabetes were identified and confirmed during 1990–2004 and 1,254 matched control subjects were selected .  Plasma leptin and sOB-R levels were measured among these participants . RESULTS After multivariate adjustment for BMI , lifestyle practice s , and dietary factors , sOB-R levels were significantly associated with a lower risk of type 2 diabetes . In comparison with women in the lowest quintile , the ORs ( 95 % CI ) of developing type 2 diabetes were 0.73 ( 0.55–0.96 ) , 0.51 ( 0.38–0.68 ) , 0.42 ( 0.31–0.57 ) , and 0.39 ( 0.28–0.54 ; P for trend < 0.0001 ) for women in the second to fifth quintiles of sOB-R levels , respectively . In contrast , plasma leptin levels were not significantly associated with the risk of type 2 diabetes : The OR ( 95 % CI ) was 0.82 ( 0.62–1.10 ; P for trend = 0.46 ) comparing the highest with the lowest quintile of leptin levels . sOB-R levels were consistently associated with a decreased risk of type 2 diabetes at various levels of leptin or high-molecular-weight adiponectin . CONCLUSIONS These data suggest a strong inverse association between plasma sOB-R levels and risk of type 2 diabetes , independent of BMI , leptin , and adiponectin levels OBJECTIVE To evaluate the associations between  adiponectin levels and 1 ) the risk of developing gestational diabetes mellitus ( GDM ) , and 2 ) insulin resistance/sensitivity , β-cell function , and compensation indices in a prospect i ve cohort representative of the general population of pregnant women . RESEARCH DESIGN AND METHODS We performed anthropometric measurements and collected blood sample s at 1st ( 6–13 weeks ) and 2nd ( 24–28 weeks ) trimesters . Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test ( International Association of the Diabetes and Pregnancy Study Groups criteria ) .  Insulin was measured ( ELISA ; Luminex ) to estimate homeostasis model assessment of insulin resistance ( HOMA-IR ) , β-cell function ( HOMA-B ) , insulin sensitivity ( Matsuda index ) , insulin secretion ( AUCinsulin/glucose ) , and β-cell compensation ( insulin secretion sensitivity index-2 ) . Adiponectin  was measured by radioimmunoassay . RESULTS Among the 445 participants included in this study , 38 women developed GDM . Women who developed GDM had lower 1st-trimester adiponectin levels ( 9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance ) . Lower adiponectin levels were associated with higher risk of developing GDM ( OR , 1.12 per 1 µg/mL decrease of adiponectin levels ; P = 0.02 , adjusted for BMI and HbA1c at 1st trimester ) . Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR ( both : r = −0.22 , P < 0.0001 ) and Matsuda index ( r = 0.28 , P < 0.0001 , and r = 0.29 , P < 0.0001 ) . After adjustment for confounding factors , we found no significant association with HOMA-B and AUCinsulin/glucose . CONCLUSIONS Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements Background : Adiponectin has anti-inflammatory and insulin-sensitizing properties . Prospect i ve studies have consistently shown a lower risk of type 2 diabetes among those with higher circulating adiponectin levels . Objective : We examined prospect ively the association between serum adiponectin levels and type 2 diabetes risk among Japanese workers , taking visceral fat mass into account . Subjects and methods : Subjects were 4591 Japanese employees who attended a comprehensive health screening in 2008 ; had biochemical data including serum adiponectin ; were free of diabetes at baseline ; and received health screening in 2011 .  Multiple logistic regression analysis was used to examine the association between adiponectin and incidence of diabetes among overall subjects , as well as subgroups . Stratified analyses were carried out according to variables including visceral fat area ( VFA ) . Results : During 3 years of follow-up , 217 diabetic cases were newly identified . Of these , 87 % had a prediabetes at baseline . Serum adiponectin level was significantly , inversely associated with incidence of diabetes , with odds ratios ( 95 % confidence interval ) adjusted for age , sex , family history , smoking , alcohol drinking , physical activity and body mass index ( BMI ) for the lowest through highest quartile of adiponectin of 1 ( reference ) , 0.79 ( 0.55–1.12 ) , 0.60 ( 0.41–0.88 ) and 0.40 ( 0.25–0.64 ) , respectively ( P-value for trend < 0.01 ) . This association was material ly unchanged with adjustment for VFA instead of BMI . After further adjustment for both homeostasis model assessment of insulin resistance and hemoglo 
    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: Screening for glucose intolerance during pregnancy provides an opportunity to offer management to those women diagnosed with gestational diabetes mellitus . However , there is a need to diagnose gestational diabetes early to minimize exposure of the developing fetus to suboptimal conditions and prevent perinatal complications and their sequelae . The purpose of this study was to identify potential biomarkers for impending gestational diabetes that appear in the plasma before impaired glucose tolerance . Pregnant women were prospect ively recruited to the study and blood was collected at the first antenatal visit and at the time of routine oral glucose tolerance test . Women diagnosed with gestational diabetes were matched with an equal number of normal pregnant ( control ) women . Biomarkers under investigation included endocrine and metabolic hormones , cytokines and chemokines , and surrogate markers of oxidative stress . Compared to controls , women with gestational diabetes exhibited elevated plasma insulin and reduced plasma adiponectin concentrations at 28 weeks gestation . Significant differences in insulin and adiponectin concentrations were also observed in plasma at 11 weeks gestation . Bivariate logistic regression analysis showed that both insulin and adiponectin are associated with subsequent development of gestational diabetes . Plasma insulin and adiponectin concentrations , when measured at 11 weeks , may be predictive of impending gestational diabetes . Further studies are warranted to determine the reliability of these biomarkers OBJECTIVE : Emerging evidence suggests that leptin , an adipocyte-derived hormone , may have independent direct effects on both insulin secretion and action , in addition to its well documented effects on appetite and energy expenditure . Some , but not all , previously published studies suggest that maternal leptin concentrations may be increased in pregnancies complicated by gestational diabetes mellitus ( GDM ) . We examined the association between plasma leptin concentration and GDM risk . METHODS : Women were recruited before 16 weeks of gestation and were followed up until delivery .  Maternal plasma leptin concentrations  ( collected at 13 weeks of gestation ) were measured by using immunoassay . We used generalized linear models to estimate relative risks and 95 % confidence intervals . RESULTS : GDM developed in 5.7 % of the cohort ( 47 of 823 ) . Elevated leptin concentrations were positively associated with GDM risk ( P for trend < .001 ) . After adjusting for maternal prepregnancy adiposity and other confounders , women with leptin concentrations of 31.0 ng/mL or higher experienced a 4.7-fold increased risk of GDM ( 95 % confidence interval 1.2 , 18.0 ) as compared with women who had concentrations of 14.3 ng/mL or lower . We noted a strong linear component of trend in risk of GDM with increasing maternal plasma leptin concentration . Each 10-ng/mL increase in the leptin concentration was associated with a 20 % increase in GDM risk ( relative risk 1.2 ; 95 % confidence interval 1.0 , 1.3 ) . CONCLUSIONS : Hyperleptinemia , independent of maternal adiposity , in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy . Additional larger prospect i ve cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy . LEVEL OF EVIDENCE : AIM To examine the prediction of gestational diabetes in obese women using routine clinical measures and measurement of biomarkers related to insulin resistance in the early second trimester . METHODS A total of 117 obese pregnant women participating in a pilot trial of a complex intervention of dietary advice and physical activity  were studied . Blood sample s were obtained at recruitment ( 15⁺⁰-17⁺⁶ weeks ' gestation ) and demographic , clinical history and anthropometric measures recorded . The biomarkers analysed were plasma lipids ( HDL cholesterol , LDL cholesterol , triglycerides ) , high-sensitivity C-reactive protein , alanine transaminase , aspartate transaminase , ferritin , fructosamine , insulin , adiponectin , tissue plasminogen activator , interleukin-6 , visfatin and leptin . Univariate and logistic regression analyses were performed to determine independent predictors and area under the receiver-operating curve was calculated for the model . RESULTS Of the 106 participants included in the analysis , 29 ( 27.4 % ) developed gestational diabetes . Participants with gestational diabetes were older ( P = 0.002 ) , more often of parity ≥ 2 , had higher systolic ( P = 0.02 ) and diastolic blood pressure ( P = 0.02 ) and were more likely to be black ( P = 0.009 ) . Amongst the blood biomarkers measured , plasma adiponectin alone remained independently associated with gestational diabetes in adjusted models ( P = 0.002 ) . The area under the receiver-operating curve for clinical factors alone ( 0.760 ) increased significantly ( area under the curve 0.834 , chi-square statistic ( 1 ) = 4.00 , P = 0.046 ) with the addition of adiponectin . CONCLUSIONS A combination of routinely measured clinical factors and adiponectin measured in the early second trimester in obese women may provide a useful approach to the prediction of gestational diabetes . Validation in a large prospect i ve study is required to determine the usefulness of this algorithm in clinical practice Nuala Sheehan and colleagues describe how Mendelian r and omization provides an alternative way of dealing with the problems of observational studies , especially confounding OBJECTIVE To develop a model for the prediction of gestational diabetes mellitus ( GDM ) from maternal characteristics and biochemical markers at 11 to 13 weeks ' gestation . METHODS A prospect i ve screening study on early prediction of pregnancy complications ( n = 11 , 464 ) , including 297 ( 2.6 % ) cases of GDM was used to create the predictive model of GDM based on maternal characteristics .  Maternal serum concentrations of adiponectin , follistatin-like-3 ( FSTL3 ) and sex hormone-binding globulin ( SHBG ) were measured in a case-control study of 80 women who developed GDM and 300 controls . RESULTS In the screening study , maternal age , body mass index , racial origin , previous history of GDM and macrosomic neonate were significant independent predictors of future GDM . In the GDM group , compared to controls , the median multiple of the normal median adiponectin ( 0.66 ; IQR : 0.5 - 0.9 vs 1.02 ; IQR : 0.7 - 1.29 ) and SHBG ( 0.81 ; IQR : 0.6 - 1.04 vs 1.02 ; IQR : 0.8 - 1.2 ) was lower ( p < 0.05 ) , but FSTL3 was not significantly different . In screening for GDM by maternal characteristics , the detection rate was 61.6 % at a false-positive rate of 20 % and the detection increased to 74.1 % by the addition of adiponectin and SHBG . CONCLUSION First-trimester screening for GDM can be provided by a combination of maternal characteristics and biomarkers OBJECTIVE We prospect ively examined plasma levels of leptin and soluble leptin receptor ( sOB-R ) , as well as their interactions with other diabetes risk factors , in relation to type 2 diabetes to eluci date the complex relation between these two biomarkers and diabetes risk . RESEARCH DESIGN AND METHODS Of 32,826 Nurses ' Health Study participants who provided blood sample s during 1989–1990 , 1,054 incident case subjects of type 2 diabetes were identified and confirmed during 1990–2004 and 1,254 matched control subjects were selected .  Plasma leptin and sOB-R levels were measured among these participants . RESULTS After multivariate adjustment for BMI , lifestyle practice s , and dietary factors , sOB-R levels were significantly associated with a lower risk of type 2 diabetes . In comparison with women in the lowest quintile , the ORs ( 95 % CI ) of developing type 2 diabetes were 0.73 ( 0.55–0.96 ) , 0.51 ( 0.38–0.68 ) , 0.42 ( 0.31–0.57 ) , and 0.39 ( 0.28–0.54 ; P for trend < 0.0001 ) for women in the second to fifth quintiles of sOB-R levels , respectively . In contrast , plasma leptin levels were not significantly associated with the risk of type 2 diabetes : The OR ( 95 % CI ) was 0.82 ( 0.62–1.10 ; P for trend = 0.46 ) comparing the highest with the lowest quintile of leptin levels . sOB-R levels were consistently associated with a decreased risk of type 2 diabetes at various levels of leptin or high-molecular-weight adiponectin . CONCLUSIONS These data suggest a strong inverse association between plasma sOB-R levels and risk of type 2 diabetes , independent of BMI , leptin , and adiponectin levels OBJECTIVE To evaluate the associations between  adiponectin levels and 1 ) the risk of developing gestational diabetes mellitus ( GDM ) , and 2 ) insulin resistance/sensitivity , β-cell function , and compensation indices in a prospect i ve cohort representative of the general population of pregnant women . RESEARCH DESIGN AND METHODS We performed anthropometric measurements and collected blood sample s at 1st ( 6–13 weeks ) and 2nd ( 24–28 weeks ) trimesters . Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test ( International Association of the Diabetes and Pregnancy Study Groups criteria ) .  Insulin was measured ( ELISA ; Luminex ) to estimate homeostasis model assessment of insulin resistance ( HOMA-IR ) , β-cell function ( HOMA-B ) , insulin sensitivity ( Matsuda index ) , insulin secretion ( AUCinsulin/glucose ) , and β-cell compensation ( insulin secretion sensitivity index-2 ) . Adiponectin  was measured by radioimmunoassay . RESULTS Among the 445 participants included in this study , 38 women developed GDM . Women who developed GDM had lower 1st-trimester adiponectin levels ( 9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance ) . Lower adiponectin levels were associated with higher risk of developing GDM ( OR , 1.12 per 1 µg/mL decrease of adiponectin levels ; P = 0.02 , adjusted for BMI and HbA1c at 1st trimester ) . Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR ( both : r = −0.22 , P < 0.0001 ) and Matsuda index ( r = 0.28 , P < 0.0001 , and r = 0.29 , P < 0.0001 ) . After adjustment for confounding factors , we found no significant association with HOMA-B and AUCinsulin/glucose . CONCLUSIONS Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements Background : Adiponectin has anti-inflammatory and insulin-sensitizing properties . Prospect i ve studies have consistently shown a lower risk of type 2 diabetes among those with higher circulating adiponectin levels . Objective : We examined prospect ively the association between serum adiponectin levels and type 2 diabetes risk among Japanese workers , taking visceral fat mass into account . Subjects and methods : Subjects were 4591 Japanese employees who attended a comprehensive health screening in 2008 ; had biochemical data including serum adiponectin ; were free of diabetes at baseline ; and received health screening in 2011 .  Multiple logistic regression analysis was used to examine the association between adiponectin and incidence of diabetes among overall subjects , as well as subgroups . Stratified analyses were carried out according to variables including visceral fat area ( VFA ) . Results : During 3 years of follow-up , 217 diabetic cases were newly identified . Of these , 87 % had a prediabetes at baseline . Serum adiponectin level was significantly , inversely associated with incidence of diabetes , with odds ratios ( 95 % confidence interval ) adjusted for age , sex , family history , smoking , alcohol drinking , physical activity and body mass index ( BMI ) for the lowest through highest quartile of adiponectin of 1 ( reference ) , 0.79 ( 0.55–1.12 ) , 0.60 ( 0.41–0.88 ) and 0.40 ( 0.25–0.64 ) , respectively ( P-value for trend < 0.01 ) . This association was material ly unchanged with adjustment for VFA instead of BMI . After further adjustment for both homeostasis model assessment of insulin resistance and hemoglo 
    Output:
    