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: Objectives . The prevalence of type 2 diabetes in American adolescents has increased markedly during the past generation . Although the factors that contribute to the development of type 2 diabetes are complex and not wholly eluci date d , the triad of severe obesity , hyperinsulinemia , and a family history of type 2 diabetes places a child at an increased risk for development of the disease . Current approaches to the prevention of type 2 diabetes , including dietary counseling and exercise , have had limited success . We reasoned that drugs that increase glucose tolerance in diabetic patients might prove useful in preventing the progression to glucose intolerance in high-risk patients . To that end , we conducted a double-blind , placebo-controlled study of the effects of metformin  on body mass index ( BMI ) , serum leptin , glucose tolerance , and serum lipids in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes . Methods . The study population consisted of 29 white and black adolescents aged 12 to 19 years . All had BMI s exceeding 30 kg/m2 . Criteria for enrollment included : 1 ) a fasting insulin concentration exceeding 15 μU/mL ; and 2 ) at least 1 first- or second-degree relative with type 2 diabetes . All patients had fasting plasma glucose concentrations < 110 mg% and hemoglobin A1c concentrations ≤6.0 % . All had normal linear growth and sexual development for age , with no marked hirsutism , severe acne , or menstrual irregularities characteristic of polycystic ovary syndrome . Eight participants had acanthosis nigricans . After baseline laboratory studies including a rapidly sample d intravenous glucose tolerance test , patients were r and omized to receive metformin ( 500 mg twice daily ) or a placebo for a total of 6 months . The effects of metformin  on BMI st and ard deviation score , serum leptin , glucose tolerance , and serum lipids were analyzed . The study was double-blinded and included no specific dietary restrictions . Results . Metformin caused a decline of 0.12 st and ard deviation in BMI in study participants ( −1.3 % from baseline ) , and a 5.5 % reduction in serum leptin in girls . In contrast , BMI and serum leptin rose 0.23 st and ard deviation ( 2.3 % ) and 16.2 % , respectively , in the placebo group during the treatment period . Metformin caused a progressive decline in fasting blood glucose ( from a mean of 84.9 to 75.1 mg% ) and a reduction in fasting insulin levels ( from 31.3 to 19.3 μU/mL ) . In contrast , fasting glucose levels in the placebo group rose slightly from 77.2 to 82.3 mg% , and fasting insulin levels did not change . Insulin sensitivity , as assessed by the ratio of fasting insulin to glucose concentrations and the quantitative insulin sensitivity check index ( 1/[log fasting insulin + log fasting glucose ] ) and homeostasis model assessment insulin resistance index ( fasting insulin × fasting glucose/22.5 ) indices , increased slightly in the metformin-treated participants . However , the insulin sensitivity measured using Bergman 's minimal model did not change . There were also no significant changes in glucose effectiveness , hemoglobin A1c , serum lipids , or serum lactate in the metformin or placebo groups . Metformin was tolerated well by the majority of patients . Transient abdominal discomfort or diarrhea occurred in 40 % of treated participants ; there were no episodes of vomiting or lactic acidosis . Conclusions . The treatment of obesity and insulin resistance in adults often proves ineffective because the vicious cycle leading to type 2 diabetes may have become entrenched and , to some extent , may be irreversible . Early detection and therapy of the obese adolescent with a family history of type 2 diabetes may interrupt the cycle of weight gain and insulin resistance that leads to glucose intolerance in adulthood . Through its ability to reduce fasting blood glucose and insulin concentrations and to moderate weight gain , metformin might complement the effects of dietary and exercise counseling and reduce the risk of type 2 diabetes in selected patients OBJECTIVE The management of obesity , apart from exercise , mainly involves a calorie restriction regimen . A pharmaceutical treatment is often used to improve patient compliance and diet effectiveness , although several side-effects have previously been described . To improve patient compliance and diet effectiveness without incurring unpleasant side-effects , we evaluated whether a distracting mini-meal can physiologically decrease the absorption of fats and carbohydrates . DESIGN Two minutes before each of the three meals consumed daily , 32 obese patients were treated with a distracting mini-meal , 32 with metformin , and 32 with placebo . At baseline and after 1 , 3 , and 6 months of treatment , body weight , body mass index , waist circumference , fasting/post-pr and ial insulinaemia and glycaemia , homeostasis model assessment -index , triacylglycerols , and total cholesterol were evaluated . RESULTS All patients showed good compliance . With the exception of post-pr and ial glycaemia , a significant reduction in all parameters was documented in every group , albeit the greater variation was observed in patients treated with a distracting mini-meal or metformin . No one showed noteworthy side-effects . CONCLUSIONS Our study focuses on a distracting mini-meal that could become a useful tool in enhancing weight loss . The beneficial effect of a distracting meal on insulin resistance , glucose , and lipid metabolism suggest its possible use to prevent or mitigate obesity-related disorders Objectives : Obesity and hypertension are associated with an adverse metabolic profile and systemic low- grade inflammation . Metformin reduces weight and inflammation in patients with diabetes , but it is unclear whether it has beneficial effects in patients without diabetes . The objective was to explore whether metformin-based treatment could benefit obesity-related hypertension without diabetes . Methods : A r and omized , double-blind , placebo-controlled factorial trial was conducted in 360 obese hypertensive patients without diabetes in Chongqing , China . After a 1–2-week run-in period , patients were r and omly assigned to metformin ( 500 mg once per day ) or placebo , as well as to an antihypertensive medication .  Change in blood pressure , obesity measurements and metabolic profile were assessed at 24 weeks . Results : The 180 participants r and omized to metformin and 180 r and omized to placebo were similar at baseline . At 24 weeks , metformin compared with placebo did not have significant effects on blood pressure , blood glucose , high-density or low-density lipoprotein cholesterol , but it did reduce total serum cholesterol ( 0.27mmol/l , P = 0.038 ) . Metformin also significantly reduced weight ( −0.7 kg , P = 0.006 ) , BMI ( −0.2 kg/m2 , P = 0.024 ) , waist circumference ( −0.9 cm , P = 0.008 ) , and both subcutaneous ( −6.1 cm2 , P = 0.043 ) and visceral adiposity ( −5.4 cm2 , P = 0.028 ) as measured by computed tomography , and lowered serum high-sensitivity C-reactive protein levels ( −0.6 mg/dl , P < 0.001 ) . There was no significant difference in adverse events ( P = 0.785 ) . Conclusions : Metformin has no effect on blood pressure and blood glucose levels , but it does reduce total cholesterol , abdominal obesity and C-reactive protein levels in obese hypertensive patients without diabetes This study assessed the efficacy of adding metformin to a structured lifestyle intervention in reducing BMI in obese adolescents with insulin resistance . Obese adolescents ( 25 ) aged 10–16 years with a body mass index ( BMI ) > 95th percentile and insulin resistance ( Homeostasis Model Assessment —HOMA ) > 3.0 were assessed in a community clinic . A structured lifestyle intervention comprising nutritional and exercise education and motivational support in both individual and group sessions was delivered over 6 months . Subjects were r and omized to lifestyle intervention alone or with metformin ( 1500 g daily ) . The primary outcome measures were a change in BMI and modification of metabolic risk factors , including insulin resistance , plasma lipids and adipocytokines .  Eleven adolescents receiving lifestyle and metformin intervention and 14 receiving lifestyle alone completed the study .  BMI decreased by 1.8 kg/m2 with lifestyle and metformin but did not change with lifestyle alone . HOMA was significantly decreased in the lifestyle intervention group , but not following metformin , while the adiponectin/leptin ratio improved significantly in both groups . Dyslipidemic profiles improved most significantly with metformin . We conclude that metformin in combination with a 6-month structured lifestyle intervention is effective in reducing BMI in obese adolescents but did not improve insulin resistance . Lifestyle intervention , with or without metformin , improved metabolic risk factors such as plasma lipids and adipocytokines Objective : To study the long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance . Patients : 181 African American subjects with insulin resistance and normal glucose tolerance test were r and omised to receive glipizide 5 mg/day ( n = 25 ) , metformin 500 mg/day ( n = 59 ) , or placebo ( n = 97 ) for 24 months . Insulin sensitivity , glucose tolerance , lipid profile , left ventricular mass ( echocardiography ) , aortic distensibility ( echocardiography , blood pressure ) , aortic pulse wave velocity ( PWV , carotid to femoral artery , Doppler ) were measured at baseline and at 12 and 24 months after r and omisation . Results : A significant increase in PWV was observed in both glipizide ( mean ( SEM ) change at 24 months 2.8 ( 2.7 ) m/s , p = 0.012 ) and metformin ( 2.2 ( 0.7 ) m/s , p = 0.01 ) groups during the follow up period . In contrast , PWV remained unchanged in the placebo group . The increase in PWV in the treatment groups was significant compared with placebo ( analysis of variance p < 0.05 ) . Other cardiovascular or metabolic variables did not change significantly compared with placebo during follow up . Conclusions : The observed increase in PWV is consistent with a decrease in the elastic properties of the aorta . The use of oral antidiabetic agents for the prevention of cardiovascular complications in non-diabetic African Americans with insulin resistance needs to be critically evaluated 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 
    Output:
    
agent
Network meta- analysis revealed that in adolescents , intervention with 2000 mg/day metformin ranked better than other interventions ; however , 1000 mg/day metformin for 3 months may be most suitable for adolescents .
For adults , metformin at doses of 3000 and 1000 mg/day ranked the highest , other than minimeal and lifestyle interventions ; moreover , intervention with 3000 mg/day for 6 months and 1000 mg/day for 0.5 months may be suitable for adults .
Conclusion When considering the efficacy of interventions for losing weight , metformin offers clear advantages for overweight and obese population
***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: Objectives . The prevalence of type 2 diabetes in American adolescents has increased markedly during the past generation . Although the factors that contribute to the development of type 2 diabetes are complex and not wholly eluci date d , the triad of severe obesity , hyperinsulinemia , and a family history of type 2 diabetes places a child at an increased risk for development of the disease . Current approaches to the prevention of type 2 diabetes , including dietary counseling and exercise , have had limited success . We reasoned that drugs that increase glucose tolerance in diabetic patients might prove useful in preventing the progression to glucose intolerance in high-risk patients . To that end , we conducted a double-blind , placebo-controlled study of the effects of metformin  on body mass index ( BMI ) , serum leptin , glucose tolerance , and serum lipids in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes . Methods . The study population consisted of 29 white and black adolescents aged 12 to 19 years . All had BMI s exceeding 30 kg/m2 . Criteria for enrollment included : 1 ) a fasting insulin concentration exceeding 15 μU/mL ; and 2 ) at least 1 first- or second-degree relative with type 2 diabetes . All patients had fasting plasma glucose concentrations < 110 mg% and hemoglobin A1c concentrations ≤6.0 % . All had normal linear growth and sexual development for age , with no marked hirsutism , severe acne , or menstrual irregularities characteristic of polycystic ovary syndrome . Eight participants had acanthosis nigricans . After baseline laboratory studies including a rapidly sample d intravenous glucose tolerance test , patients were r and omized to receive metformin ( 500 mg twice daily ) or a placebo for a total of 6 months . The effects of metformin  on BMI st and ard deviation score , serum leptin , glucose tolerance , and serum lipids were analyzed . The study was double-blinded and included no specific dietary restrictions . Results . Metformin caused a decline of 0.12 st and ard deviation in BMI in study participants ( −1.3 % from baseline ) , and a 5.5 % reduction in serum leptin in girls . In contrast , BMI and serum leptin rose 0.23 st and ard deviation ( 2.3 % ) and 16.2 % , respectively , in the placebo group during the treatment period . Metformin caused a progressive decline in fasting blood glucose ( from a mean of 84.9 to 75.1 mg% ) and a reduction in fasting insulin levels ( from 31.3 to 19.3 μU/mL ) . In contrast , fasting glucose levels in the placebo group rose slightly from 77.2 to 82.3 mg% , and fasting insulin levels did not change . Insulin sensitivity , as assessed by the ratio of fasting insulin to glucose concentrations and the quantitative insulin sensitivity check index ( 1/[log fasting insulin + log fasting glucose ] ) and homeostasis model assessment insulin resistance index ( fasting insulin × fasting glucose/22.5 ) indices , increased slightly in the metformin-treated participants . However , the insulin sensitivity measured using Bergman 's minimal model did not change . There were also no significant changes in glucose effectiveness , hemoglobin A1c , serum lipids , or serum lactate in the metformin or placebo groups . Metformin was tolerated well by the majority of patients . Transient abdominal discomfort or diarrhea occurred in 40 % of treated participants ; there were no episodes of vomiting or lactic acidosis . Conclusions . The treatment of obesity and insulin resistance in adults often proves ineffective because the vicious cycle leading to type 2 diabetes may have become entrenched and , to some extent , may be irreversible . Early detection and therapy of the obese adolescent with a family history of type 2 diabetes may interrupt the cycle of weight gain and insulin resistance that leads to glucose intolerance in adulthood . Through its ability to reduce fasting blood glucose and insulin concentrations and to moderate weight gain , metformin might complement the effects of dietary and exercise counseling and reduce the risk of type 2 diabetes in selected patients OBJECTIVE The management of obesity , apart from exercise , mainly involves a calorie restriction regimen . A pharmaceutical treatment is often used to improve patient compliance and diet effectiveness , although several side-effects have previously been described . To improve patient compliance and diet effectiveness without incurring unpleasant side-effects , we evaluated whether a distracting mini-meal can physiologically decrease the absorption of fats and carbohydrates . DESIGN Two minutes before each of the three meals consumed daily , 32 obese patients were treated with a distracting mini-meal , 32 with metformin , and 32 with placebo . At baseline and after 1 , 3 , and 6 months of treatment , body weight , body mass index , waist circumference , fasting/post-pr and ial insulinaemia and glycaemia , homeostasis model assessment -index , triacylglycerols , and total cholesterol were evaluated . RESULTS All patients showed good compliance . With the exception of post-pr and ial glycaemia , a significant reduction in all parameters was documented in every group , albeit the greater variation was observed in patients treated with a distracting mini-meal or metformin . No one showed noteworthy side-effects . CONCLUSIONS Our study focuses on a distracting mini-meal that could become a useful tool in enhancing weight loss . The beneficial effect of a distracting meal on insulin resistance , glucose , and lipid metabolism suggest its possible use to prevent or mitigate obesity-related disorders Objectives : Obesity and hypertension are associated with an adverse metabolic profile and systemic low- grade inflammation . Metformin reduces weight and inflammation in patients with diabetes , but it is unclear whether it has beneficial effects in patients without diabetes . The objective was to explore whether metformin-based treatment could benefit obesity-related hypertension without diabetes . Methods : A r and omized , double-blind , placebo-controlled factorial trial was conducted in 360 obese hypertensive patients without diabetes in Chongqing , China . After a 1–2-week run-in period , patients were r and omly assigned to metformin ( 500 mg once per day ) or placebo , as well as to an antihypertensive medication .  Change in blood pressure , obesity measurements and metabolic profile were assessed at 24 weeks . Results : The 180 participants r and omized to metformin and 180 r and omized to placebo were similar at baseline . At 24 weeks , metformin compared with placebo did not have significant effects on blood pressure , blood glucose , high-density or low-density lipoprotein cholesterol , but it did reduce total serum cholesterol ( 0.27mmol/l , P = 0.038 ) . Metformin also significantly reduced weight ( −0.7 kg , P = 0.006 ) , BMI ( −0.2 kg/m2 , P = 0.024 ) , waist circumference ( −0.9 cm , P = 0.008 ) , and both subcutaneous ( −6.1 cm2 , P = 0.043 ) and visceral adiposity ( −5.4 cm2 , P = 0.028 ) as measured by computed tomography , and lowered serum high-sensitivity C-reactive protein levels ( −0.6 mg/dl , P < 0.001 ) . There was no significant difference in adverse events ( P = 0.785 ) . Conclusions : Metformin has no effect on blood pressure and blood glucose levels , but it does reduce total cholesterol , abdominal obesity and C-reactive protein levels in obese hypertensive patients without diabetes This study assessed the efficacy of adding metformin to a structured lifestyle intervention in reducing BMI in obese adolescents with insulin resistance . Obese adolescents ( 25 ) aged 10–16 years with a body mass index ( BMI ) > 95th percentile and insulin resistance ( Homeostasis Model Assessment —HOMA ) > 3.0 were assessed in a community clinic . A structured lifestyle intervention comprising nutritional and exercise education and motivational support in both individual and group sessions was delivered over 6 months . Subjects were r and omized to lifestyle intervention alone or with metformin ( 1500 g daily ) . The primary outcome measures were a change in BMI and modification of metabolic risk factors , including insulin resistance , plasma lipids and adipocytokines .  Eleven adolescents receiving lifestyle and metformin intervention and 14 receiving lifestyle alone completed the study .  BMI decreased by 1.8 kg/m2 with lifestyle and metformin but did not change with lifestyle alone . HOMA was significantly decreased in the lifestyle intervention group , but not following metformin , while the adiponectin/leptin ratio improved significantly in both groups . Dyslipidemic profiles improved most significantly with metformin . We conclude that metformin in combination with a 6-month structured lifestyle intervention is effective in reducing BMI in obese adolescents but did not improve insulin resistance . Lifestyle intervention , with or without metformin , improved metabolic risk factors such as plasma lipids and adipocytokines Objective : To study the long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance . Patients : 181 African American subjects with insulin resistance and normal glucose tolerance test were r and omised to receive glipizide 5 mg/day ( n = 25 ) , metformin 500 mg/day ( n = 59 ) , or placebo ( n = 97 ) for 24 months . Insulin sensitivity , glucose tolerance , lipid profile , left ventricular mass ( echocardiography ) , aortic distensibility ( echocardiography , blood pressure ) , aortic pulse wave velocity ( PWV , carotid to femoral artery , Doppler ) were measured at baseline and at 12 and 24 months after r and omisation . Results : A significant increase in PWV was observed in both glipizide ( mean ( SEM ) change at 24 months 2.8 ( 2.7 ) m/s , p = 0.012 ) and metformin ( 2.2 ( 0.7 ) m/s , p = 0.01 ) groups during the follow up period . In contrast , PWV remained unchanged in the placebo group . The increase in PWV in the treatment groups was significant compared with placebo ( analysis of variance p < 0.05 ) . Other cardiovascular or metabolic variables did not change significantly compared with placebo during follow up . Conclusions : The observed increase in PWV is consistent with a decrease in the elastic properties of the aorta . The use of oral antidiabetic agents for the prevention of cardiovascular complications in non-diabetic African Americans with insulin resistance needs to be critically evaluated 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 
    Output:
    