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: Abstract Aim : Glucagon-like peptide 1 receptor agonists ( GLP-1 RA ) stimulate satiety leading to reductions in food intake and body weight . The effects of long- acting GLP-1 RA liraglutide on eating behavior of women with PCOS have not been investigated yet . Methods : Thirty-six obese women with PCOS ( mean ± SD , aged 31.2 ± 7.8 years , with BMI 38.7 ± 0.1 kg/m2 ) , pretreated with metformin ( 1000 mg BID ) were switched to liraglutide 1.2 mg QD sc for 12 weeks . Adiposity parameters and eating behavior as assessed by Three-Factor Eating Question naire ( TFEQ-R18 ) were examined at baseline and after 12 weeks . Results : Subjects treated with liraglutide lost on average 3.8 ± 0.1 kg ( p < 0.001 ) . Significant reductions of waist circumference and visceral adipose tissue ( VAT ) mass , volume and area were demonstrated from liraglutide induction to the end of the study . TFEQ-R18 scores were significantly different pre- and post-liraglutide intervention . After treatment with liraglutide  the uncontrolled eating ( UE ) score decreased from 36.8 ± 24.5 to 19.6 ± 18.4 ( p < 0.001 ) and emotional eating ( EE ) score decreased from 49.9 ± 33.3 to 28.5 ± 26.9 ( p < 0.001 ) . Scores for cognitive restraint ( CR ) were not changed . Conclusions : Short-term liraglutide treatment was associated with weight loss and significantly improved eating behavior in obese women with PCOS BACKGROUND Investigation of a possible effect of metformin on and rogen levels in pregnant women with polycystic ovary syndrome ( PCOS ) . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled pilot study was conducted . Forty pregnant women with PCOS received diet and lifestyle counselling  and were r and omized to either metformin 850 mg twice daily or placebo . Primary outcome measures were changes in serum levels of dehydroepi and rosterone sulphate , and rostenedione , testosterone , sex hormone-binding globulin , and free testosterone index . Secondary outcome measures were pregnancy complications and outcome . Two-tailed t-tests and chi2-tests were used . RESULTS Maternal and rogen levels were unaffected by metformin treatment in pregnant women with PCOS . While none of the 18 women in the metformin group experienced a severe pregnancy or post-partum complication , seven of the 22 ( 32 % ) women experienced severe complications in the placebo group ( P = 0.01 ) . CONCLUSIONS Metformin treatment did not reduce maternal and rogen levels in pregnant women with PCOS . In the metformin-treated group we observed a reduction of severe , pregnancy and post-partum complications .  Metformin treatment of pregnant PCOS women may reduce complications during pregnancy and in the post-partum period CONTEXT Polycystic ovary syndrome ( PCOS ) presents in adolescence , and obesity is a common finding . The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear . OBJECTIVE We investigated the effects of metformin , oral contraceptives ( OCs ) , and /or lifestyle modification in obese adolescent women with PCOS . DESIGN Two small , r and omized , placebo-controlled clinical trials were performed . PATIENTS AND PARTICIPANTS A total of 79 obese adolescent women with PCOS participated . INTERVENTIONS In the single treatment trial , subjects were r and omized to metformin , placebo , a lifestyle modification program , or OC . In the combined treatment trial , all subjects received lifestyle modification and OC and were r and omized to metformin or placebo . MAIN OUTCOME MEASURES Serum concentrations of and rogens and lipids were measured . RESULTS Lifestyle modification alone result ed in a 59 % reduction in free and rogen index with a 122 % increase in SHBG . OC result ed in a significant decrease in total testosterone ( 44 % ) and free and rogen index ( 86 % ) but also result ed in an increase in C-reactive protein ( 39.7 % ) and cholesterol ( 14 % ) . The combination of lifestyle modification , OC , and metformin result ed in a 55 % decrease in total testosterone , as compared to 33 % with combined treatment and placebo , a 4 % reduction in waist circumference , and a significant increase in HDL ( 46 % ) . CONCLUSIONS In these preliminary trials , both lifestyle modification and OCs significantly reduce and rogens and increase SHBG in obese adolescents with PCOS . Metformin , in combination with lifestyle modification and OC , reduces central adiposity , reduces total testosterone , and increases HDL , but does not enhance overall weight reduction CONTEXT A past history of gestational diabetes mellitus ( GDM ) confers a very high risk of postpartum development of diabetes , particularly type 2 diabetes . OBJECTIVE The Diabetes Prevention Program ( DPP ) sought to identify individuals with impaired glucose tolerance ( IGT ) and intervene in an effort to prevent or delay their progression to diabetes . This analysis examined the differences between women enrolled in DPP with and without a reported history of GDM . DESIGN The DPP was a r and omized , controlled clinical trial . SETTING The study was a multicenter , National Institutes of Health-sponsored trial carried out at 27 centers including academic and Indian Health Services sites . PATIENTS A total of 2190 women were r and omized into the DPP and provided information for past history of GDM . This analysis addressed the differences between those 350 women providing a past history of GDM and those 1416 women with a previous live birth but no history of GDM . INTERVENTIONS Subjects were r and omized to either st and ard lifestyle and placebo or metformin therapy or to an intensive lifestyle intervention . MAIN OUTCOMES The primary outcome was the time to development of diabetes ascertained by semiannual fasting plasma glucose and annual oral glucose tolerance testing . Assessment s of insulin secretion and insulin sensitivity were also performed . RESULTS Whereas entering the study with similar glucose levels , women with a history of GDM r and omized to placebo had a crude incidence rate of diabetes 71 % higher than that of women without such a history . Among women reporting a history of GDM , both intensive lifestyle and metformin therapy reduced the incidence of diabetes by approximately 50 % compared with the placebo group , whereas this reduction was 49 and 14 % , respectively in parous women without GDM . These data suggest that metformin may be more effective in women with a GDM history as compared with those without . CONCLUSIONS Progression to diabetes is more common in women with a history of GDM compared with those without GDM history despite equivalent degrees of IGT at baseline . Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome ( PCOS ) . Dietary-induced weight loss and the administration of insulin-lowering drugs , such as metformin , are usually followed by improved hyper and rogenism and related clinical abnormalities . This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight , fat distribution , the glucose-insulin system , and hormones in a group of 20 obese PCOS women [ body mass index ( BMI ) > 28 kg/m2 ] with the abdominal phenotype ( waist to hip ratio > 0.80 ) , and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS . At baseline , we measured sex hormone , sex hormone-binding globulin ( SHBG ) , and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography ( CT ) at the L4-L5 level , to measure sc adipose tissue area ( SAT ) and visceral adipose tissue area . All women were then given a low-calorie diet ( 1,200 - 1,400 kcal/day ) alone for one month , after which anthropometric parameters and CT scan were newly measured . While continuing dietary treatment , PCOS women and obese controls were subsequently placed , in a r and om order , on metformin ( 850 mg/os , twice daily ) ( 12 and 8 , respectively ) or placebo ( 8 and 12 , respectively ) , according to a double-blind design , for the following 6 months . Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment . During the treatment period , 3 women of the control group ( all treated with placebo ) were excluded because of noncompliance ; and 2 PCOS women , both treated with metformin , were also excluded because they became pregnant . Therefore , the women cohort available for final statistical analysis included 18 PCOS ( 10 treated with metformin and 8 with placebo ) and 17 control women ( 8 treated with metformin and 9 with placebo )  . The treatment was well tolerated . In the PCOS group , metformin therapy improved hirsutism and menstrual cycles significantly more than placebo .  Baseline anthropometric and CT parameters were similar in all groups . Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups , without any significant effect on CT scan parameters . In both PCOS and control women , however , metformin treatment reduced body weight and BMI significantly more than placebo . Changes in the waist-to-hip ratio values were similar in PCOS women and controls , regardless of pharmacological treatment . Metformin treatment significantly decreased SAT values in both PCOS and control groups , although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment . On the contrary , visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups , but only in the former was the effect of metformin treatment significantly higher than that of placebo .  Fasting insulin significantly decreased in both PCOS women and controls , regardless of treatment , whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin . Neither metformin or placebo significantly modified the levels of LH , FSH , dehydroepi and rosterone sulphate , and progesterone in any group , whereas testosterone concentrations decreased only in PCOS women treated with metformin .  SHBG concentrations remained unchanged in all PCOS women ; whereas in the control group , they significantly increased after both metformin and placebo .  Leptin levels decreased only during metformin treatment in both PCOS and control groups . ( ABSTRACT TRUNCATED STUDY QUESTION What is the prevalence of insulin resistance ( IR ) and the contributions of intrinsic and extrinsic IR in women diagnosed with polycystic ovary syndrome ( PCOS ) according to the Rotterdam criteria ? SUMMARY ANSWER We report novel clamp data in Rotterdam diagnosed PCOS women , using World Health Organization criteria for IR showing that women with PCOS have a high prevalence of IR , strengthening the evidence for an aetiological role of IR in both National Institutes of Health ( NIH ) and Rotterdam diagnosed PCOS in lean and overweight women . WHAT IS KNOWN ALREADY PCOS is a complex endocrine condition with a significant increased risk of gestational diabetes and type 2 diabetes . STUDY DESIGN , SIZE , DURATION Using a cross-sectional study design , 20 overweight and 20 lean PCOS ( Rotterdam criteria ) , 14 overweight and 19 lean body mass index ( BMI ) -matched control non-PCOS women underwent clinical measures of IR after a 3-month withdrawal of insulin sensitizers and the oral contraceptive pill . MATERIAL S , SETTING , METHODS In an academic clinic setting ,  glucose infusion rate ( GIR )  on euglycaemic-hyperinsulinaemic clamp was investigated as a marker of insulin sensitivity . MAIN RESULTS AND THE ROLE OF CHANCE PCOS women were more IR than BMI -matched controls ( main effect for BMI and PCOS ; P < 0.001 ) . IR was present in 75 % of lean PCOS , 62 % of overweight controls and 95 % of overweight PCOS . Lean controls ( mean ± SD ; GIR 339 ± 76 mg min⁻¹ m⁻² ) were less IR than lean PCOS ( 270 ± 66 mg min⁻¹ m⁻² ) , overweight controls ( 264 ± 66 mg min⁻¹ m⁻² ) and overweight PCOS ( 175 ± 96 mg min⁻¹ m⁻² ) . The negative relationship between BMI and IR reflected by GIR was more marked in PCOS ( y = 445.1 - 7.7x , R² = 0.42 ( P < 0.0001 ) than controls ( y = 435.5 - 4.6x , R² = 0.04 ( P < 0.01 ) ) . LIMITATIONS , REASONS FOR CAUTION The 
    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: Abstract Aim : Glucagon-like peptide 1 receptor agonists ( GLP-1 RA ) stimulate satiety leading to reductions in food intake and body weight . The effects of long- acting GLP-1 RA liraglutide on eating behavior of women with PCOS have not been investigated yet . Methods : Thirty-six obese women with PCOS ( mean ± SD , aged 31.2 ± 7.8 years , with BMI 38.7 ± 0.1 kg/m2 ) , pretreated with metformin ( 1000 mg BID ) were switched to liraglutide 1.2 mg QD sc for 12 weeks . Adiposity parameters and eating behavior as assessed by Three-Factor Eating Question naire ( TFEQ-R18 ) were examined at baseline and after 12 weeks . Results : Subjects treated with liraglutide lost on average 3.8 ± 0.1 kg ( p < 0.001 ) . Significant reductions of waist circumference and visceral adipose tissue ( VAT ) mass , volume and area were demonstrated from liraglutide induction to the end of the study . TFEQ-R18 scores were significantly different pre- and post-liraglutide intervention . After treatment with liraglutide  the uncontrolled eating ( UE ) score decreased from 36.8 ± 24.5 to 19.6 ± 18.4 ( p < 0.001 ) and emotional eating ( EE ) score decreased from 49.9 ± 33.3 to 28.5 ± 26.9 ( p < 0.001 ) . Scores for cognitive restraint ( CR ) were not changed . Conclusions : Short-term liraglutide treatment was associated with weight loss and significantly improved eating behavior in obese women with PCOS BACKGROUND Investigation of a possible effect of metformin on and rogen levels in pregnant women with polycystic ovary syndrome ( PCOS ) . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled pilot study was conducted . Forty pregnant women with PCOS received diet and lifestyle counselling  and were r and omized to either metformin 850 mg twice daily or placebo . Primary outcome measures were changes in serum levels of dehydroepi and rosterone sulphate , and rostenedione , testosterone , sex hormone-binding globulin , and free testosterone index . Secondary outcome measures were pregnancy complications and outcome . Two-tailed t-tests and chi2-tests were used . RESULTS Maternal and rogen levels were unaffected by metformin treatment in pregnant women with PCOS . While none of the 18 women in the metformin group experienced a severe pregnancy or post-partum complication , seven of the 22 ( 32 % ) women experienced severe complications in the placebo group ( P = 0.01 ) . CONCLUSIONS Metformin treatment did not reduce maternal and rogen levels in pregnant women with PCOS . In the metformin-treated group we observed a reduction of severe , pregnancy and post-partum complications .  Metformin treatment of pregnant PCOS women may reduce complications during pregnancy and in the post-partum period CONTEXT Polycystic ovary syndrome ( PCOS ) presents in adolescence , and obesity is a common finding . The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear . OBJECTIVE We investigated the effects of metformin , oral contraceptives ( OCs ) , and /or lifestyle modification in obese adolescent women with PCOS . DESIGN Two small , r and omized , placebo-controlled clinical trials were performed . PATIENTS AND PARTICIPANTS A total of 79 obese adolescent women with PCOS participated . INTERVENTIONS In the single treatment trial , subjects were r and omized to metformin , placebo , a lifestyle modification program , or OC . In the combined treatment trial , all subjects received lifestyle modification and OC and were r and omized to metformin or placebo . MAIN OUTCOME MEASURES Serum concentrations of and rogens and lipids were measured . RESULTS Lifestyle modification alone result ed in a 59 % reduction in free and rogen index with a 122 % increase in SHBG . OC result ed in a significant decrease in total testosterone ( 44 % ) and free and rogen index ( 86 % ) but also result ed in an increase in C-reactive protein ( 39.7 % ) and cholesterol ( 14 % ) . The combination of lifestyle modification , OC , and metformin result ed in a 55 % decrease in total testosterone , as compared to 33 % with combined treatment and placebo , a 4 % reduction in waist circumference , and a significant increase in HDL ( 46 % ) . CONCLUSIONS In these preliminary trials , both lifestyle modification and OCs significantly reduce and rogens and increase SHBG in obese adolescents with PCOS . Metformin , in combination with lifestyle modification and OC , reduces central adiposity , reduces total testosterone , and increases HDL , but does not enhance overall weight reduction CONTEXT A past history of gestational diabetes mellitus ( GDM ) confers a very high risk of postpartum development of diabetes , particularly type 2 diabetes . OBJECTIVE The Diabetes Prevention Program ( DPP ) sought to identify individuals with impaired glucose tolerance ( IGT ) and intervene in an effort to prevent or delay their progression to diabetes . This analysis examined the differences between women enrolled in DPP with and without a reported history of GDM . DESIGN The DPP was a r and omized , controlled clinical trial . SETTING The study was a multicenter , National Institutes of Health-sponsored trial carried out at 27 centers including academic and Indian Health Services sites . PATIENTS A total of 2190 women were r and omized into the DPP and provided information for past history of GDM . This analysis addressed the differences between those 350 women providing a past history of GDM and those 1416 women with a previous live birth but no history of GDM . INTERVENTIONS Subjects were r and omized to either st and ard lifestyle and placebo or metformin therapy or to an intensive lifestyle intervention . MAIN OUTCOMES The primary outcome was the time to development of diabetes ascertained by semiannual fasting plasma glucose and annual oral glucose tolerance testing . Assessment s of insulin secretion and insulin sensitivity were also performed . RESULTS Whereas entering the study with similar glucose levels , women with a history of GDM r and omized to placebo had a crude incidence rate of diabetes 71 % higher than that of women without such a history . Among women reporting a history of GDM , both intensive lifestyle and metformin therapy reduced the incidence of diabetes by approximately 50 % compared with the placebo group , whereas this reduction was 49 and 14 % , respectively in parous women without GDM . These data suggest that metformin may be more effective in women with a GDM history as compared with those without . CONCLUSIONS Progression to diabetes is more common in women with a history of GDM compared with those without GDM history despite equivalent degrees of IGT at baseline . Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome ( PCOS ) . Dietary-induced weight loss and the administration of insulin-lowering drugs , such as metformin , are usually followed by improved hyper and rogenism and related clinical abnormalities . This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight , fat distribution , the glucose-insulin system , and hormones in a group of 20 obese PCOS women [ body mass index ( BMI ) > 28 kg/m2 ] with the abdominal phenotype ( waist to hip ratio > 0.80 ) , and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS . At baseline , we measured sex hormone , sex hormone-binding globulin ( SHBG ) , and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography ( CT ) at the L4-L5 level , to measure sc adipose tissue area ( SAT ) and visceral adipose tissue area . All women were then given a low-calorie diet ( 1,200 - 1,400 kcal/day ) alone for one month , after which anthropometric parameters and CT scan were newly measured . While continuing dietary treatment , PCOS women and obese controls were subsequently placed , in a r and om order , on metformin ( 850 mg/os , twice daily ) ( 12 and 8 , respectively ) or placebo ( 8 and 12 , respectively ) , according to a double-blind design , for the following 6 months . Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment . During the treatment period , 3 women of the control group ( all treated with placebo ) were excluded because of noncompliance ; and 2 PCOS women , both treated with metformin , were also excluded because they became pregnant . Therefore , the women cohort available for final statistical analysis included 18 PCOS ( 10 treated with metformin and 8 with placebo ) and 17 control women ( 8 treated with metformin and 9 with placebo )  . The treatment was well tolerated . In the PCOS group , metformin therapy improved hirsutism and menstrual cycles significantly more than placebo .  Baseline anthropometric and CT parameters were similar in all groups . Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups , without any significant effect on CT scan parameters . In both PCOS and control women , however , metformin treatment reduced body weight and BMI significantly more than placebo . Changes in the waist-to-hip ratio values were similar in PCOS women and controls , regardless of pharmacological treatment . Metformin treatment significantly decreased SAT values in both PCOS and control groups , although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment . On the contrary , visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups , but only in the former was the effect of metformin treatment significantly higher than that of placebo .  Fasting insulin significantly decreased in both PCOS women and controls , regardless of treatment , whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin . Neither metformin or placebo significantly modified the levels of LH , FSH , dehydroepi and rosterone sulphate , and progesterone in any group , whereas testosterone concentrations decreased only in PCOS women treated with metformin .  SHBG concentrations remained unchanged in all PCOS women ; whereas in the control group , they significantly increased after both metformin and placebo .  Leptin levels decreased only during metformin treatment in both PCOS and control groups . ( ABSTRACT TRUNCATED STUDY QUESTION What is the prevalence of insulin resistance ( IR ) and the contributions of intrinsic and extrinsic IR in women diagnosed with polycystic ovary syndrome ( PCOS ) according to the Rotterdam criteria ? SUMMARY ANSWER We report novel clamp data in Rotterdam diagnosed PCOS women , using World Health Organization criteria for IR showing that women with PCOS have a high prevalence of IR , strengthening the evidence for an aetiological role of IR in both National Institutes of Health ( NIH ) and Rotterdam diagnosed PCOS in lean and overweight women . WHAT IS KNOWN ALREADY PCOS is a complex endocrine condition with a significant increased risk of gestational diabetes and type 2 diabetes . STUDY DESIGN , SIZE , DURATION Using a cross-sectional study design , 20 overweight and 20 lean PCOS ( Rotterdam criteria ) , 14 overweight and 19 lean body mass index ( BMI ) -matched control non-PCOS women underwent clinical measures of IR after a 3-month withdrawal of insulin sensitizers and the oral contraceptive pill . MATERIAL S , SETTING , METHODS In an academic clinic setting ,  glucose infusion rate ( GIR )  on euglycaemic-hyperinsulinaemic clamp was investigated as a marker of insulin sensitivity . MAIN RESULTS AND THE ROLE OF CHANCE PCOS women were more IR than BMI -matched controls ( main effect for BMI and PCOS ; P < 0.001 ) . IR was present in 75 % of lean PCOS , 62 % of overweight controls and 95 % of overweight PCOS . Lean controls ( mean ± SD ; GIR 339 ± 76 mg min⁻¹ m⁻² ) were less IR than lean PCOS ( 270 ± 66 mg min⁻¹ m⁻² ) , overweight controls ( 264 ± 66 mg min⁻¹ m⁻² ) and overweight PCOS ( 175 ± 96 mg min⁻¹ m⁻² ) . The negative relationship between BMI and IR reflected by GIR was more marked in PCOS ( y = 445.1 - 7.7x , R² = 0.42 ( P < 0.0001 ) than controls ( y = 435.5 - 4.6x , R² = 0.04 ( P < 0.01 ) ) . LIMITATIONS , REASONS FOR CAUTION The 
    Output:
    