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: BACKGROUND The association between birthweight and subsequent blood pressure levels  has been considered to provide some of the strongest , and most consistent , support for the " fetal origins " hypothesis of adult disease . It had been estimated that a 1 kg higher birthweight is typically associated with a 2 - 4 mm Hg lower systolic blood pressure . METHODS 55 studies that had reported regression coefficients of systolic blood pressure on birthweight ( with 48 further studies that reported only the direction of this association ) , and seven such studies within twin pairs , were identified . Each study was weighted according to the inverse of the variance of the regression coefficient ( ie , " statistical size " ) , and combined using a " fixed effects " approach . FINDINGS Among the 55 studies that reported regression coefficients , there was a clear trend ( p<0.0001 ) towards weaker associations in the larger studies : -1.9 mm Hg/kg in those with less than about 1000 participants ; -1.5 mm Hg/kg with about 1000 - 3000 participants ; and -0.6 mm Hg/kg with more than 3000 participants . By contrast with the inverse associations reported in 52 of these 55 studies , only 25 of the 48 studies that did not report regression coefficients found an inverse association ( p<0.0001 for heterogeneity ) . Almost all of these regression coefficients had been adjusted for current weight ( whereas few were adjusted for potential confounding factors ) , and removal of this adjustment in the larger studies reduced the estimated association to -0.4 mm Hg/kg . For studies within monozygotic twin pairs , the combined estimate was -0.6 mm Hg/kg with adjustment for current weight , and was also reduced without this adjustment . INTERPRETATION Cl aims of a strong inverse association between birthweight and subsequent blood pressure may chiefly reflect the impact of r and om error , selective emphasis of particular results , and inappropriate adjustment for current weight and for confounding factors . These findings suggest that birthweight is of little relevance to blood pressure levels in later life AIMS To describe the prevalence of impaired glucose tolerance and obesity in offspring of mothers whose pregnancies were complicated by gestational diabetes mellitus ( GDM ) in a low-risk population and to investigate the effect on these outcomes of minimal intervention compared with tight control for management of GDM . METHODS Eighty-nine children ( mean age 9.1 years , 93 % Caucasian ) were recruited through a follow-up study of women previously involved in a r and omized controlled trial of minimal intervention ( control group ) vs. tight glycaemic control ( treatment group ) for GDM . Fasting blood glucose ( FBG ) and 2-h glucose tolerance tests ( 2hGTT ) were performed on offspring and body mass index ( BMI ) calculated . Glucose tolerance and BMI of treatment groups were compared using non-inferiority tests ( non-inferiority margin -15 % ) . RESULTS Of those offspring , 6.9 % ( 5/72 ) had abnormal glucose metabolism [ four children had impaired glucose tolerance ( IGT ) and one had Type 2 diabetes mellitus ( DM ) ( all Caucasian ) ] . Of the four children with IGT , three were male , three had normal BMI , and three had a family history of Type 2 diabetes . Of the 71 offspring who underwent 2hGTT , 25/25 ( 100 % ) of the control offspring and 46/46 ( 100 % ) of the treatment offspring had normal FBG ( FBG < 5.7 mmol/l ) . Twenty-five of 25 ( 100 % ) of control and 42/46 ( 91.3 % ) of the treatment offspring had normal glucose tolerance ( 2hGTT < 7.8 mmol/l ) ( % difference 8.7 , 95 % CI -5.6 , 20.3 ) . BMI < 85th percentile was found in 25/33 ( 75.8 % ) of the treatment group and 44/52 ( 84.6 % ) of the control group ( difference in percentage -8.9 , 95 % CI -27.2 , 7.8 ) . CONCLUSIONS School-age children of mothers with GDM are at risk of IGT and overweight , even if from a low-risk ethnic population . FBG was not adequate for screening this population . Minimal intervention for glycaemic control in GDM pregnancies appears to be as effective as tight control for preventing IGT in childhood but not for preventing obesity To examine whether poor growth in utero or young childhood is associated with adult abdominal fatness in a developing country context , the authors analyzed prospect ively collected data on 372 female and 161 male Guatemalans measured as children between 1969 and 1977 and remeasured as adults in 1988 - 1989 ( men and women ) and 1991 - 1994 ( women only ) . Childhood stunting ( height-for-age z score ) was associated with a lower body mass index and percent body fat in men , while no associations were found in women . In both sexes , however , severely stunted children had significantly greater adult abdominal fatness ( waist : hip ratio ) , once overall fatness and confounders were controlled . The adult waist : hip ratio ( x100 ) was increased by 0.65 ( 95 % confidence interval 0.10 to 1.20 ) in men and 0.29 ( 95 % confidence interval -0.03 to 0.61 ) in women for each height-for-age z score less at age three . Migration to urban centers was significantly associated with an even greater waist : hip ratio in severely stunted females ( p = 0.03 ) . In a sub sample of 137 women , short and thin newborns had significantly greater adult abdominal fatness compared with long and thin or short and fat newborns or children who became stunted postnatally . The adult waist : hip ratio ( x100 ) was increased by 1.58 ( 95 % confidence interval 0.35 to 2.81 ) for each kilogram less birth weight . The authors conclude that , in countries where maternal and child malnutrition exists alongside rapid economic development and urban migration , abdominal obesity and related chronic diseases are likely to increase Given the growing recognition of the importance of the life course approach for the determination of chronic diseases , birth cohort studies are becoming increasingly important . This paper describes the methods used in the 1982 Pelotas ( Brazil ) birth cohort study  , one of the largest and longest studies of this type in developing countries . All 5,914 hospital births occurring in Pelotas in 1982 ( over 99 % of all deliveries ) were studied prospect ively . The main stages of the study took place in 1983 , 1984 , 1986 , 1995 , 1997 , 2000 , and 2001 . More than two thous and variables are available for each subject who participated in all stages of the study . Recent phases of the study included the examination of 2,250 males when presenting for the army recruitment exam in 2000 , the study of a 27 % sample of men and women in 2001 through household visits , and the study of over 400 children born to the cohort women .  Follow-up rates in the recent stages of the cohort were 78.9 % for the army examination and 69.0 % for the household visits . Ethnographic and oral health studies were conducted in sub- sample s. Some recent results on blood pressure , adolescent pregnancy , and asthma are presented as examples of utilization of the data . Suggestions on lessons learned for other cohort studies are proposed Low birth weight is associated with increased cardiovascular and metabolic disorders in adult life , although the mechanisms of this effect remain uncertain . There is one report of increased morning plasma cortisol levels in an elderly low birth weight cohort , but whether this is primary or secondary to other aspects of the phenotype is unclear . We investigated the association between low birth weight and glucose intolerance , blood pressure , and dyslipidemia in young , nonobese adults from a community undergoing the health transition with a high prevalence of both noncommunicable diseases and low birth weight . Additionally , we investigated whether altered basal and stimulated cortisol levels as a marker of hypothalamic-pituitary-adrenal responsiveness or cortisol metabolism were associated with low birth weight in these young adults . Twenty-year-old , historically disadvantaged , urbanized South Africans ( n = 137 ) with birth weights either below the 10th percentile [ underweight for age ( UFA ) ] or between the 25th and 75th percentiles [ appropriate for gestational age ( AFA ) ] had anthropometry , blood pressure , lipid levels , and glucose tolerance measured . In a subset ( n = 62 ) , 0900 h plasma cortisol concentrations , cortisol responses to 1 microg ACTH , and urinary glucocorticoid metabolites were measured . The mothers of UFA infants were themselves lighter and had a lower body mass index ( P : = 0 . 0016 ) . At age 20 yr , although the UFA group was still smaller and lighter , with a lower body mass index , they had higher fasting plasma glucose levels ( P : = 0.047 ) , and a greater proportion demonstrated glucose intolerance ( 11.9 % vs. 0 % ; P : < 0.01 ) . The UFA group also had higher systolic [ UFA , 126.0 + /- 13.3 ( + /-SD ) ; AFA , 122.0 + /- 11.7 mm Hg ; P : = 0.007 ] and diastolic ( 72.3 + /- 8.4 vs. 69 . 5 + /- 8.7 mm Hg ; P : = 0.02 ) blood pressures , after covarying for current weight and gender . Plasma cortisol levels determined at 0900 h were higher in the UFA group ( 484.9 + /- 166.3 vs. 418.6 + /- 160.6 nmol/L ) and showed a greater plasma cortisol response to low dose ACTH stimulation ( area under the curve for cortisol : UFA , 77,238 + /- 19,511 ; AFA , 66,597 + /- 16,064 nmol/L.min ; P : = 0.04 ) . In conclusion , the link between low birth weight and adult glucose intolerance and blood pressure elevation occurs in young adults in a high risk , disadvantaged population despite a lack of full catch-up growth . Moreover , cortisol axis activation is an early feature in the process linking low birth weight with adult cardiovascular and metabolic disease and is not dependent upon adult obesity or full catch-up growth , at least in this population undergoing the health transition Environmental factors and diet are generally believed to be accelerators of obesity and hypertension , but they are not the underlying cause . Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming . Using fetal undernutrition throughout pregnancy , we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease . Virgin Wistar rats were time mated and r and omly assigned to receive food either ad libitum ( AD group ) or at 30 % of ad libitum intake , or undernutrition ( UN group ) . Offspring from UN mothers were significantly smaller at birth than AD offspring . At weaning , offspring were assigned to one of two diets [ a control diet or a hypercaloric ( 30 % fat ) diet ] . Food intake in offspring from UN mothers was significantly elevated at an early postnatal age . It increased further with advancing age and was amplified by hypercaloric nutrition . UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations . This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology . We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia , obesity , and hypertension as a consequence of altered fetal development BACKGROUND Adult body size and composition ( ABSC ) measures are associated with work capacity and productivity , reproductive performance , and chronic disease risk . Growth failure in early childhood may have important long-term consequences through its influence on ABSC . OBJECTIVE We assessed associations between prenatal and postnatal growth ( 0 - 2 y of age ) and ABSC . DESIGN We included 267 singletons from a prospect i ve study carried out between 1969 and 1977 in 4 ladino Guatemalan villages . We used data from that study and from a follow-up study conducted in 1998 - 1999 ( when the subjects were 21 - 27 y of age ) to determine associations of birth weight , length at 15 d of age , ponderal index , and length at 2 y of age with adult height , weight , fat-free mass ( FFM ) , fat mass , percentage of body fat , and waist-to-hip ratio . Multivariate linear regression analyses with mixed models were carried out to account for sibling clustering . Two-stage least-squares analyses were used to separate specific effects of prenatal and postnatal growth . RESULTS Birth weight , length at 15 d of age , and length at 2 y of age were positively associated with height , weight , and FFM in both sexes ( P < 0.0 
    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: BACKGROUND The association between birthweight and subsequent blood pressure levels  has been considered to provide some of the strongest , and most consistent , support for the " fetal origins " hypothesis of adult disease . It had been estimated that a 1 kg higher birthweight is typically associated with a 2 - 4 mm Hg lower systolic blood pressure . METHODS 55 studies that had reported regression coefficients of systolic blood pressure on birthweight ( with 48 further studies that reported only the direction of this association ) , and seven such studies within twin pairs , were identified . Each study was weighted according to the inverse of the variance of the regression coefficient ( ie , " statistical size " ) , and combined using a " fixed effects " approach . FINDINGS Among the 55 studies that reported regression coefficients , there was a clear trend ( p<0.0001 ) towards weaker associations in the larger studies : -1.9 mm Hg/kg in those with less than about 1000 participants ; -1.5 mm Hg/kg with about 1000 - 3000 participants ; and -0.6 mm Hg/kg with more than 3000 participants . By contrast with the inverse associations reported in 52 of these 55 studies , only 25 of the 48 studies that did not report regression coefficients found an inverse association ( p<0.0001 for heterogeneity ) . Almost all of these regression coefficients had been adjusted for current weight ( whereas few were adjusted for potential confounding factors ) , and removal of this adjustment in the larger studies reduced the estimated association to -0.4 mm Hg/kg . For studies within monozygotic twin pairs , the combined estimate was -0.6 mm Hg/kg with adjustment for current weight , and was also reduced without this adjustment . INTERPRETATION Cl aims of a strong inverse association between birthweight and subsequent blood pressure may chiefly reflect the impact of r and om error , selective emphasis of particular results , and inappropriate adjustment for current weight and for confounding factors . These findings suggest that birthweight is of little relevance to blood pressure levels in later life AIMS To describe the prevalence of impaired glucose tolerance and obesity in offspring of mothers whose pregnancies were complicated by gestational diabetes mellitus ( GDM ) in a low-risk population and to investigate the effect on these outcomes of minimal intervention compared with tight control for management of GDM . METHODS Eighty-nine children ( mean age 9.1 years , 93 % Caucasian ) were recruited through a follow-up study of women previously involved in a r and omized controlled trial of minimal intervention ( control group ) vs. tight glycaemic control ( treatment group ) for GDM . Fasting blood glucose ( FBG ) and 2-h glucose tolerance tests ( 2hGTT ) were performed on offspring and body mass index ( BMI ) calculated . Glucose tolerance and BMI of treatment groups were compared using non-inferiority tests ( non-inferiority margin -15 % ) . RESULTS Of those offspring , 6.9 % ( 5/72 ) had abnormal glucose metabolism [ four children had impaired glucose tolerance ( IGT ) and one had Type 2 diabetes mellitus ( DM ) ( all Caucasian ) ] . Of the four children with IGT , three were male , three had normal BMI , and three had a family history of Type 2 diabetes . Of the 71 offspring who underwent 2hGTT , 25/25 ( 100 % ) of the control offspring and 46/46 ( 100 % ) of the treatment offspring had normal FBG ( FBG < 5.7 mmol/l ) . Twenty-five of 25 ( 100 % ) of control and 42/46 ( 91.3 % ) of the treatment offspring had normal glucose tolerance ( 2hGTT < 7.8 mmol/l ) ( % difference 8.7 , 95 % CI -5.6 , 20.3 ) . BMI < 85th percentile was found in 25/33 ( 75.8 % ) of the treatment group and 44/52 ( 84.6 % ) of the control group ( difference in percentage -8.9 , 95 % CI -27.2 , 7.8 ) . CONCLUSIONS School-age children of mothers with GDM are at risk of IGT and overweight , even if from a low-risk ethnic population . FBG was not adequate for screening this population . Minimal intervention for glycaemic control in GDM pregnancies appears to be as effective as tight control for preventing IGT in childhood but not for preventing obesity To examine whether poor growth in utero or young childhood is associated with adult abdominal fatness in a developing country context , the authors analyzed prospect ively collected data on 372 female and 161 male Guatemalans measured as children between 1969 and 1977 and remeasured as adults in 1988 - 1989 ( men and women ) and 1991 - 1994 ( women only ) . Childhood stunting ( height-for-age z score ) was associated with a lower body mass index and percent body fat in men , while no associations were found in women . In both sexes , however , severely stunted children had significantly greater adult abdominal fatness ( waist : hip ratio ) , once overall fatness and confounders were controlled . The adult waist : hip ratio ( x100 ) was increased by 0.65 ( 95 % confidence interval 0.10 to 1.20 ) in men and 0.29 ( 95 % confidence interval -0.03 to 0.61 ) in women for each height-for-age z score less at age three . Migration to urban centers was significantly associated with an even greater waist : hip ratio in severely stunted females ( p = 0.03 ) . In a sub sample of 137 women , short and thin newborns had significantly greater adult abdominal fatness compared with long and thin or short and fat newborns or children who became stunted postnatally . The adult waist : hip ratio ( x100 ) was increased by 1.58 ( 95 % confidence interval 0.35 to 2.81 ) for each kilogram less birth weight . The authors conclude that , in countries where maternal and child malnutrition exists alongside rapid economic development and urban migration , abdominal obesity and related chronic diseases are likely to increase Given the growing recognition of the importance of the life course approach for the determination of chronic diseases , birth cohort studies are becoming increasingly important . This paper describes the methods used in the 1982 Pelotas ( Brazil ) birth cohort study  , one of the largest and longest studies of this type in developing countries . All 5,914 hospital births occurring in Pelotas in 1982 ( over 99 % of all deliveries ) were studied prospect ively . The main stages of the study took place in 1983 , 1984 , 1986 , 1995 , 1997 , 2000 , and 2001 . More than two thous and variables are available for each subject who participated in all stages of the study . Recent phases of the study included the examination of 2,250 males when presenting for the army recruitment exam in 2000 , the study of a 27 % sample of men and women in 2001 through household visits , and the study of over 400 children born to the cohort women .  Follow-up rates in the recent stages of the cohort were 78.9 % for the army examination and 69.0 % for the household visits . Ethnographic and oral health studies were conducted in sub- sample s. Some recent results on blood pressure , adolescent pregnancy , and asthma are presented as examples of utilization of the data . Suggestions on lessons learned for other cohort studies are proposed Low birth weight is associated with increased cardiovascular and metabolic disorders in adult life , although the mechanisms of this effect remain uncertain . There is one report of increased morning plasma cortisol levels in an elderly low birth weight cohort , but whether this is primary or secondary to other aspects of the phenotype is unclear . We investigated the association between low birth weight and glucose intolerance , blood pressure , and dyslipidemia in young , nonobese adults from a community undergoing the health transition with a high prevalence of both noncommunicable diseases and low birth weight . Additionally , we investigated whether altered basal and stimulated cortisol levels as a marker of hypothalamic-pituitary-adrenal responsiveness or cortisol metabolism were associated with low birth weight in these young adults . Twenty-year-old , historically disadvantaged , urbanized South Africans ( n = 137 ) with birth weights either below the 10th percentile [ underweight for age ( UFA ) ] or between the 25th and 75th percentiles [ appropriate for gestational age ( AFA ) ] had anthropometry , blood pressure , lipid levels , and glucose tolerance measured . In a subset ( n = 62 ) , 0900 h plasma cortisol concentrations , cortisol responses to 1 microg ACTH , and urinary glucocorticoid metabolites were measured . The mothers of UFA infants were themselves lighter and had a lower body mass index ( P : = 0 . 0016 ) . At age 20 yr , although the UFA group was still smaller and lighter , with a lower body mass index , they had higher fasting plasma glucose levels ( P : = 0.047 ) , and a greater proportion demonstrated glucose intolerance ( 11.9 % vs. 0 % ; P : < 0.01 ) . The UFA group also had higher systolic [ UFA , 126.0 + /- 13.3 ( + /-SD ) ; AFA , 122.0 + /- 11.7 mm Hg ; P : = 0.007 ] and diastolic ( 72.3 + /- 8.4 vs. 69 . 5 + /- 8.7 mm Hg ; P : = 0.02 ) blood pressures , after covarying for current weight and gender . Plasma cortisol levels determined at 0900 h were higher in the UFA group ( 484.9 + /- 166.3 vs. 418.6 + /- 160.6 nmol/L ) and showed a greater plasma cortisol response to low dose ACTH stimulation ( area under the curve for cortisol : UFA , 77,238 + /- 19,511 ; AFA , 66,597 + /- 16,064 nmol/L.min ; P : = 0.04 ) . In conclusion , the link between low birth weight and adult glucose intolerance and blood pressure elevation occurs in young adults in a high risk , disadvantaged population despite a lack of full catch-up growth . Moreover , cortisol axis activation is an early feature in the process linking low birth weight with adult cardiovascular and metabolic disease and is not dependent upon adult obesity or full catch-up growth , at least in this population undergoing the health transition Environmental factors and diet are generally believed to be accelerators of obesity and hypertension , but they are not the underlying cause . Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming . Using fetal undernutrition throughout pregnancy , we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease . Virgin Wistar rats were time mated and r and omly assigned to receive food either ad libitum ( AD group ) or at 30 % of ad libitum intake , or undernutrition ( UN group ) . Offspring from UN mothers were significantly smaller at birth than AD offspring . At weaning , offspring were assigned to one of two diets [ a control diet or a hypercaloric ( 30 % fat ) diet ] . Food intake in offspring from UN mothers was significantly elevated at an early postnatal age . It increased further with advancing age and was amplified by hypercaloric nutrition . UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations . This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology . We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia , obesity , and hypertension as a consequence of altered fetal development BACKGROUND Adult body size and composition ( ABSC ) measures are associated with work capacity and productivity , reproductive performance , and chronic disease risk . Growth failure in early childhood may have important long-term consequences through its influence on ABSC . OBJECTIVE We assessed associations between prenatal and postnatal growth ( 0 - 2 y of age ) and ABSC . DESIGN We included 267 singletons from a prospect i ve study carried out between 1969 and 1977 in 4 ladino Guatemalan villages . We used data from that study and from a follow-up study conducted in 1998 - 1999 ( when the subjects were 21 - 27 y of age ) to determine associations of birth weight , length at 15 d of age , ponderal index , and length at 2 y of age with adult height , weight , fat-free mass ( FFM ) , fat mass , percentage of body fat , and waist-to-hip ratio . Multivariate linear regression analyses with mixed models were carried out to account for sibling clustering . Two-stage least-squares analyses were used to separate specific effects of prenatal and postnatal growth . RESULTS Birth weight , length at 15 d of age , and length at 2 y of age were positively associated with height , weight , and FFM in both sexes ( P < 0.0 
    Output:
    