OBJECTIVES: To describe average levels of free-living energy expenditure in people from affluent societies and to determine the influence of body weight, height, age and sex. DESIGN: Analysis of 574 measurements of total energy expenditure (TEE, assessed by the doubly-labelled water method); basal metabolic rate (BMR, directly measured or derived from similar directly measured proxy measures such as during sleep); activity energy expenditure (AEE, derived as TEE-BMR); and physical activity level (PAL, derived as TEE/BMR) from people aged 2-95 years. The dataset was extracted from 1614 published and unpublished measurements in 1156 subjects after exclusion of repeat estimates and subjects in special physiological or behavioural states (eg pregnancy, athletic or military training etc). RESULTS: A separate analysis of data from non-ambulant subjects, and from elite endurance athletes (all excluded from the main dataset) established the limits of human daily energy expenditure at around 1.2 x BMR and 4.5 x BMR. In the main analysis, the validity of PAL as an index of TEE adjusted for BMR was tested and confirmed. Regression equations were then derived to describe TEE, BMR, AEE and PAL in terms of body weight, height, age and sex. As anticipated, TEE, BMR and AEE were all positively related to weight and height, while age was a negative predictor, especially of activity. The influence of weight disappeared when TEE was expressed as PAL, but height and age remained as highly significant predictors. For all three components, females expended 11% less energy on average than males after adjustment for weight, height and age. Average levels of energy expenditure in different age and sex groups are tabulated. CONCLUSIONS: There now exists a large and robust database of energy expenditure measurements obtained by the doubly-labelled water method. Analysis of the data from affluent societies shows that, in general, levels of energy expenditure are similar to the recommendations for energy requirements adopted by FAO/WHO/UNU (1985) and UK Department of Health (1991). PAL values for active subjects tend to be higher than is currently assumed. The current analysis provides a substantial body of normal data against which other estimates can be compared.

Adolescent↗

PubMed1996

Energy expenditure in overweight and obese adults in affluent societies: an analysis of 319 doubly-labelled water measurements.

OBJECTIVES: To describe the relationship between graded levels of obesity and free-living energy expenditure in men and women in affluent societies. DESIGN: Analysis of 319 measurements of energy expenditure in adults aged 18-64 years. The variables analysed were: total energy expenditure (TEE, assessed by the doubly-labelled water method); measured basal metabolic rate (BMR); activity energy expenditure (AEE, derived as TEE-BMR); and physical activity level (PAL, derived as TEE/BMR). Results were analysed according to four categories of body mass index (BMI): < 25.0, 25.0-29.9, 30.0-35.0 and > 35.0 kg/m2. RESULTS: TEE increased steadily with increasing BMI (9.5 to 13.5 MJ/d in women, 12.9 to 17.5 MJ/d in men, ANOVA, P < 0.0001 for both sexes). BMR also increased (5.7 to 8.2 MJ/d in women, 7.2 to 11.6 MJ/d in men, P < 0.0001 for both). AEE increased steadily in women (3.8 to 5.3 MJ/d, P < 0.0003), but in men increased up to the third BMI category (5.7 to 7.5 MJ/d, n.s.) and then declined in the most obese group (5.9 MJ/d, n.s.). The increases in energy expenditure were not in direct proportion to body weight since, when expressed per kg, both TEE and AEE declined significantly with increasing BMI. PAL remained quite constant across the three lowest BMI groups, indicating similar levels of physical activity. There was a non-significant decrease in PAL in the most obese men and women. CONCLUSIONS: This analysis confirms that habitual energy expenditure is substantially and progressively raised in obesity. It contradicts the claim, based on self-reported food intake, that obesity develops and is maintained in spite of very low levels of energy intake. The analysis suggests that, except in massive obesity, patterns of physical activity are quite similar at different levels of BMI. This does not exclude the possibility that an inactive lifestyle may be an important general risk factor for the development of obesity.

Adolescent↗

PubMed1995

Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation.

The role of the glucocorticoid receptor (GR) in glucocorticoid physiology and during development was investigated by generation of GR-deficient mice by gene targeting. GR -/- mice die within a few hours after birth because of respiratory failure. The lungs at birth are severely atelectatic, and development is impaired from day 15.5 p.c. Newborn livers have a reduced capacity to activate genes for key gluconeogenic enzymes. Feedback regulation via the hypothalamic-pituitary-adrenal axis is severely impaired resulting in elevated levels of plasma adrenocorticotrophic hormone (15-fold) and plasma corticosterone (2.5-fold). Accordingly, adrenal glands are enlarged because of hypertrophy of the cortex, resulting in increased expression of key cortical steroid biosynthetic enzymes, such as side-chain cleavage enzyme, steroid 11 beta-hydroxylase, and aldosterone synthase. Adrenal glands lack a central medulla and synthesize no adrenaline. They contain no adrenergic chromaffin cells and only scattered noradrenergic chromaffin cells even when analyzed from the earliest stages of medulla development. These results suggest that the adrenal medulla may be formed from two different cell populations: adrenergic-specific cells that require glucocorticoids for proliferation and/or survival, and a smaller noradrenergic population that differentiates normally in the absence of glucocorticoid signaling.

Adrenal Cortex↗

PubMed1995

Analysis of perinatal gene expression: hormone response elements mediate activation of a lacZ reporter gene in liver of transgenic mice.

The transcription of genes encoding gluconeogenic enzymes is tightly regulated during the perinatal period. These genes are induced by glucagon (cAMP) and glucocorticoids and repressed by insulin. To address the role of cAMP and glucocorticoids in the physiological activation of genes encoding gluconeogenic enzymes in the perinatal period, transgenic mice have been generated with chimeric constructs containing the reporter gene lacZ under the control of hormone response elements. The activity of the transgene is restricted to the liver by the presence of the enhancers from the alpha-fetoprotein gene and its transcription is driven by a promoter that contains a TATA box linked to either cAMP response elements (CREs) or glucocorticoid response elements (GREs). We demonstrate cAMP and glucocorticoid regulation, liver-specific expression, and perinatal activation of the reporter gene. These data indicate that the CRE and GRE are, independently, necessary and sufficient to mediate perinatal gene activation. Perinatal activation was not impaired when a CRE reporter transgene was assayed in mice that contain a targeted mutation of the CRE-binding protein (CREB) gene, providing further evidence for functional redundancy among the members of the CREB/ATF gene family.

Animals↗

PubMed1995

Molecular genetic analysis of glucocorticoid signaling during mouse development.

Glucocorticoids are important in a number of developmental processes in mammals around birth. The pathway of gluconeogenesis is activated in liver shortly after birth due to the combined effects of glucocorticoids and glucagon. We have defined the essential cis-regulatory elements directing hormone-dependent liver-specific expression of the gene for tyrosine aminotransferase, a key gluconeogenic enzyme. The hormone response elements synergize with cell-type specific elements. In the case of glucocorticoids, the glucocorticoid-dependent enhancer is composed of the glucocorticoid response element and binding sites for liver cell-enriched transcription factors, in particular hepatocyte nuclear factor-3. The dependence of the respective enhancer motifs on each other restricts the hormonal activation of the tyrosine aminotransferase gene in liver in response to a hormonal signal. To further understand the role of glucocorticoid signaling via the type II glucocorticoid receptor (GR) in the perinatal period and earlier during development, we have studied the expression of the mouse GR gene. Expression of the gene is controlled by at least three promoters, one of which is only active in T-lymphocytes. Expression of GR mRNA has been detected as early as day 9.5 of mouse development. To specifically address the role of glucocorticoid signaling via the GR during development, we have disrupted the GR gene by homologous recombination in mouse embryonic stem cells. The majority of GR mutants die shortly after birth and analysis so far has revealed defects in lung, liver, and adrenal function.

Animals↗

PubMed1995

Molecular genetic analysis of glucocorticoid signalling in development.

A null mutation of the glucocorticoid receptor was generated by homologous recombination. Mutant newborn mice showed impaired lung development, hypertrophy of the adrenal cortex and a strongly reduced size of the adrenal medulla. Phenylethanolamine N-methyltransferase (PNMT) was undetectable in the adrenals of the mutant mice. Serum levels of corticosterone were moderately and ACTH levels were strongly elevated in the mutants. A weaker but significant increase of corticosterone and ACTH was observed already in heterozygous animals. This points to a dysregulation of the HPA axis due to defective feedback regulation via the glucocorticoid receptor. Liver gluconeogenetic enzymes were reduced to a variable degree. Whereas survival of heterozygous mutants was not affected, most of the homozygous mutant mice died during the perinatal period.

Animals↗

PubMed1995

The bone mineral content of weight-bearing bones is influenced by the ratio of sitting to standing height in elderly Gambian women.

Body size is an important predictor of bone mineral content (BMC) at various anatomical sites but the influence of relative body proportions on BMC has previously been little studied. Using single- and dual-photon absorptiometry, we measured BMC at the distal and midshaft of the radius, the neck of femur, and the lumbar spine in 190 rural West African women aged 45-84 years. After regression adjustment for age, bone width and weight, sitting height and standing height were not separate significant determinants of BMC, except at the lumbar spine (standing height, p < 0.05). However, the ratio of sitting:standing height was a significant determinant of BMC at the neck of femur and lumbar spine, but not the midshaft or distal radius. The fact that sitting:standing height ratio is a positive predictor for BMC at hip and lumbar spine may reflect a higher peak bone mass or selective conservation of mineral in weight-bearing bones in subjects with a proportionately longer torso. We do not know whether the relationship is racially determined but we recommend that this simple combination of measurements be used in further studies in subjects of all races.

Age Factors↗

PubMed1995

Molecular genetic analysis of cAMP and glucocorticoid signaling in development.

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Animals↗

PubMed1995

Validation of weighed records and other methods of dietary assessment using the 24 h urine nitrogen technique and other biological markers.

Results from analysis of 24 h urine collections, verified for completeness with para-amino benzoic acid, and blood samples collected over 1 year were compared with 16 d weighed records of all food consumed collected over the year, and with results from 24 h recalls, food-frequency questionnaires and estimated food records in 160 women. Using the weighed records, individuals were sorted into quintiles of the distribution of the urine N excretion:dietary N intake ratio (UN:DN). UN exceeded DN in the top quintile of this ratio; mean ratio UN:DN = 1.13. Individuals in this top quintile were heavier, had significantly greater body mass indices, were reportedly more restrained eaters, had significantly lower energy intake:basal metabolic rate ratios (EI:BMR), and had correlated ratios of UN:DN and EI:BMR (r -0.62). Those in the top quintile reported lower intakes of energy and energy-yielding nutrients, Ca, fats, cakes, breakfast cereals, milk and sugars than individuals in the other quintiles but not lower intakes of non-starch polysaccharides, vitamin C, vegetables, potatoes or meat. Correlations between dietary intake from weighed records and 24 h urine K were 0.74 and 0.82, and between dietary vitamin C and beta-carotene and plasma vitamin C and beta-carotene 0.86 and 0.48. Correlations between dietary N intake from weighed records and 24 h urine excretion were high (0.78-0.87). Those between N from estimated food records and urine N were r 0.60-0.70. Correlations between urine N and 24 h recalls and food-frequency questionnaires were in the order of 0.01 to 0.5. Despite problems of underreporting in overweight individuals in 20% of this sample, weighed records remained the most accurate method of dietary assessment, and only an estimated 7 d diary was able to approach this accuracy.

Basal Metabolism↗

PubMed1995

Calcium requirements of lactating Gambian mothers: effects of a calcium supplement on breast-milk calcium concentration, maternal bone mineral content, and urinary calcium excretion.

The calcium requirement for prolonged lactation was investigated in a randomized supplementation study of Gambian mothers consuming a low-calcium diet (7.1 mmol/d, or 283 mg/d). Sixty women were studied from 10 d to 78 wk of lactation, receiving calcium or placebo for the first 12 mo. The supplement increased average calcium intake by 17.9 mmol/d (714 mg/d). Supplementation had no effect on breast-milk calcium concentration or on maternal bone mineral content. Urinary calcium output was higher in supplemented than in unsupplemented mothers by 1.18 mmol/d (47 mg/d), P < or = 0.005. Longitudinal changes in urinary calcium output and bone mineral content made a substantial contribution to calcium requirements for lactation. This study suggests that, in women with low calcium intakes, there is no direct benefit from increasing calcium intake during lactation, and that physiological mechanisms operate to furnish calcium for breast-milk production.

Adolescent↗

PubMed1995

Rate of radial bone mineral accretion in healthy children.

Radial bone width and mineral content were measured in 392 healthy Cambridge children aged 6-12 years from a cohort of 420 children studied 2 years previously. The typical rate of bone mineral accretion was 0.044 g/cm/year for boys across the whole age range and 0.042 g/cm/year for girls up to a mean age of 9 years, rising rapidly thereafter in association with changes in body size. The factors best predicting bone mineral accretion rate were mean bone mineral content, mean height, height velocity, weight velocity and bone width velocity. After adjusting for anthropometry, age did not contribute to the model. These are the first available longitudinal reference data for the rate of radial bone mineral accretion in healthy children.

Anthropometry↗

PubMed1995

Pelvic ultrasound measurements in normal girls.

Pelvic ultrasound scans were carried out in 153 normal girls aged between 3 days and 14.9 years, in order to obtain reference data for ovarian volume, uterine length and uterine configuration. The right ovary was significantly larger than the left (by about 17%). Ovarian volume increased exponentially with age, over this age range. No relationship with pubertal stage (independent of age) could be demonstrated. Uterine length decreased from birth to 4 years, before steadily increasing. The fundal-cervical ratio (FCR) decreased initially then increased to lie above 1.0 by 15 years of age. A midline endometrial echo was seen in half of the subjects aged less than 6 months, but otherwise it was not seen before 11.8 years of age or at Tanner stage B2. Smoothed reference centile curves for uterine length, right and left ovarian volume were produced, allowing z scores (or SD scores) to be calculated for each measurement.

Adolescent↗

PubMed1995

Pelvic ultrasound findings in different forms of sexual precocity.

Recently produced reference curves for various ultrasound dimensions were used to retrospectively assess 67 pelvic ultrasound scans carried out at the initial presentation in girls with sexual precocity. At presentation the group with precocious puberty had significantly increased uterine lengths and ovarian volumes compared with the normal population, and a significantly increased fundal-cervical ratio. Ovarian volume was also significantly increased in therlarche and thelarche variant. The fundal-cervical ratio was significantly increased in thelarche variant. There was considerable overlap between individuals with sexual precocity and normal subjects. The ultrasound findings that best discriminated early or precocious puberty from other forms of sexual precocity were the presence of a midline endometrial echo, and a uterine length above the 97th centile for age. An entirely normal pelvic ultrasound at presentation did not rule out the possibility of precocious puberty.

Child↗

PubMed1995

Cross sectional stature and weight reference curves for the UK, 1990.

The current reference curves of stature and weight for the UK were first published in 1966 and have been used ever since despite increasing concern that they may not adequately describe the growth of present day British children. Using current data from seven sources new reference curves have been estimated from birth to 20 years for children in 1990. The great majority of the data are nationally representative. The analysis used Cole's LMS method and has produced efficient estimates of the conventional centiles and gives a good fit to the data. These curves differ from the currently used curves at key ages for both stature and weight. In view of the concerns expressed about the current curves and the differences between them and the new curves, it is proposed that the curves presented here should be adopted as the new UK reference curves.

Adolescent↗