***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 Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors . The " gold st and ard " glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo , but neither is easily implemented in large studies . Thus , it is of interest to develop a simple , accurate method for assessing insulin sensitivity that is useful for clinical investigations . We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sample d iv glucose tolerance tests on 28 nonobese , 13 obese , and 15 type 2 diabetic subjects . We obtained correlations between indexes of insulin sensitivity from glucose clamp studies ( SI(Clamp ) ) and minimal model analysis ( SI(MM ) ) that were comparable to previous reports ( r = 0.57 ) . We performed a sensitivity analysis on our data and discovered that physiological steady state values [ i.e. fasting insulin ( I(0 ) ) and glucose ( G(0 ) ) ] contain critical information about insulin sensitivity . We defined a quantitative insulin sensitivity check index ( QUICKI = 1/[log(I(0 ) ) + log(G(0 ) ) ] ) that has substantially better correlation with SI(Clamp ) ( r = 0.78 ) than the correlation we observed between SI(MM ) and SI(Clamp ) . Moreover , we observed a comparable overall correlation between QUICKI and SI(Clamp ) in a totally independent group of 21 obese and 14 nonobese subjects from another institution . We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research OBJECTIVE Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions , including abnormalities in glucose homeostasis in adolescents , but there are few data evaluating the efficacy of metformin  among younger children . Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children , who are insulin-resistant . RESEARCH DESIGN AND METHODS This study was a r and omized double-blind placebo-controlled trial consisting of 100 severely obese ( mean BMI 34.6 ± 6.6 kg/m2 ) insulin-resistant children aged 6–12 years , r and omized to 1,000 mg metformin  ( n = 53 )  or placebo  ( n = 47 ) twice daily for 6 months , followed by open-label metformin treatment  for 6 months . All children and their parents participated in a monthly dietitian-administered weight-reduction program . RESULTS Eighty-five percent completed the 6-month r and omized phase . Children prescribed metformin had significantly greater decreases in BMI ( difference −1.09 kg/m2 , CI −1.87 to −0.31 , P = 0.006 ) , body weight ( difference −3.38 kg , CI −5.2 to −1.57 , P < 0.001 ) , BMI Z score ( difference between metformin and placebo groups −0.07 , CI −0.12 to −0.01 , P = 0.02 ) , and fat mass ( difference −1.40 kg , CI −2.74 to −0.06 , P = 0.04 ) . Fasting plasma glucose ( P = 0.007 ) and homeostasis model assessment ( HOMA ) insulin resistance index ( P = 0.006 ) also improved more in metformin-treated children than in placebo-treated children . Gastrointestinal symptoms were significantly more prevalent in metformin-treated children , which limited maximal tolerated dosage in 17 % . During the 6-month open-label phase , children treated previously with placebo  decreased their BMI Z score ; those treated continuously with metformin did not significantly change BMI Z score further . CONCLUSIONS Metformin had modest but favorable effects on body weight , body composition , and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program OBJECTIVE To study whether metformin reduces obesity , homeostasis model assessment for insulin resistance index ( HOMA-IR ) , and the metabolic syndrome ( MtS ) in obese European adolescents in addition to previous unsuccessful lifestyle intervention . DESIGN AND METHODS After 6 months of multiprofessional lifestyle intervention , 70 out of 86 adolescents without improvement in body mass index ( BMI ) and HOMA-IR  were r and omized into either the placebo ( n=34 ) or the metformin group ( 2 × 500 mg/day , n=36 ) in addition to ongoing lifestyle intervention for another 6 months . RESULTS Age was 13.8 years , BMI was 33.1 kg/m(2 ) , 65 % were female , and 89 % were Caucasians . During lifestyle intervention alone , BMI and HOMA-IR deteriorated significantly . In the subsequent medication period , HOMA-IR and fasting insulin improved similarly in the placebo and metformin groups ( HOMA-IR decreased 73 vs 54 % respectively in metformin versus placebo ; P=0.048 ) , but BMI remained unchanged . The insulin sensitivity index , however , only improved in the metformin group . High fasting insulin is correlated with a subsequent BMI increase irrespective of the medication . MtS remained unchanged . CONCLUSIONS Obese European adolescents '  insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention . Most differences did not reach statistical significance , probably due to improved compliance with lifestyle intervention as a placebo effect . In addition , the metformin dose may be too low Background The efficacy of pharmacological treatment in controlling  childhood obesity  is controversial . We aim ed to compare the effects of three types of drug regimens and placebo on generalized and abdominal obesity among obese children and adolescents who did not succeed to lose weight 3 months after lifestyle modification ( diet and exercise ) . Methods This triple-masked r and omized clinical trial was conducted among 180 participants aged 10–16 years . They were assigned r and omly to 4 groups of equal number to receive metformin , fluoxetine , a combination of the two drugs , or placebo . The trial lasted for 12 weeks and participants were followed up for an additional 12-week period . Results Overall , 91.1 % ( n=164 ) of the enrolled participants completed the trial . After the 12-week trial , the body mass index decreased significantly in all groups receiving medications [ approximately −1.2 ( 0.2 ) kg/m2 , P<0.05 ] . This decrease was not significant in the placebo group . Waist circumference decreased significantly in the groups receiving metformin [ −2.1 ( 0.4 ) cm , P=0.03 ) ] as well as in the group receiving a combination therapy of metformin and fluoxetine [ −2.5 ( 0.4 ) cm , P=0.01 ) ] . In the 24-week follow-up study , these anthropometric indexes were lower than the baseline in the group that had received a combination therapy of metformin and fluoxetine . No serious drug side-effects were reported . Conclusions A limited period of such treatment may help weight control , and might be used to encourage those children who have been refractory to weight loss for continuing the non-pharmacological programs . Our findings should be confirmed in future studies with a longer follow-up period BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent 
    Output:
    
Conclusions : Short-term metformin treatment appears to moderately affect weight reduction in severely obese children and adolescents , with a concomitant improvement in fasting insulin sensitivity .