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Background: In experimental studies, a high fluid intake and a corresponding high urine volume have been shown to increase renal excretion rates of urinary free cortisol (UFF) and cortisone (UFE) in adults. We aimed to examine whether 24-h UFF and UFE excretion rates are also affected by urine volume in children., Methods: In 24-h urine samples of 100 pre-pubertal and 100 pubertal healthy children UFF, UFE, tetrahydrocortisol (THF), 5alpha-tetrahydrocortisol (5alpha-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5alpha-THF, and THE, the 3 primarily glucuronidated tetrahydrometabolites (GC3), reflects daily cortisol secretion. Associations of urine volume with outcome variables UFF, UFE, and GC3 were examined in both developmental groups using multiple regression models adjusted for sex, body weight and height., Results: Significant positive associations were observed between 24-h urine volume and UFF and UFE in both groups with the highest explained variation for UFE [partial R(2)=0.11 in pre-pubertal group (P<0.005); partial R(2)=0.15 in pubertal group (P<0.0001)]. However, for outcome GC3, urine volume was not significant in either of the groups., Conclusion: Urinary 24-h excretion rates of UFF and UFE but not of the marker of glucocorticoid secretion are affected by daily urine volume in healthy free-living children. For a specific assessment of associations of UFF and UFE with (patho)physiologically relevant factors, urine volume should be considered as a confounder.

Background: Soft drinks are thought to displace milk in diets of children and adolescents and therefore might affect variables of bone modeling and remodeling., Objective: We assessed the association between long-term consumption of several types of soft drinks and bone variables in children and adolescents., Design: Long-term dietary data from 3-d weighed dietary records collected by 228 healthy children and adolescents enrolled in the DONALD Study in 4 y of study participation were used for data analysis. Variables of bone modeling and remodeling of the radius were assessed by using peripheral quantitative computed tomography., Results: After adjustment for age, sex, total energy intake, muscle area, BMI SD scores, and growth velocity, long-term consumption of all soft drinks and uncaffeinated soft drinks was negatively associated with bone mineral content (P < 0.05), cortical area (P < 0.05), and polar strength strain index (P < 0.05), all of which reflect a combination of bone modeling and remodeling. Long-term consumption of caffeinated soft drinks was negatively associated with polar strength strain index (P < 0.01) and periosteal circumference (P < 0.05), which reflect bone modeling. Milk intake was positively associated with polar strength strain index (P < 0.05). Consumption of all soft drinks was negatively associated with total protein and milk intake, but was not associated with potential renal acid load., Conclusions: Long-term consumption of caffeinated and uncaffeinated soft drinks appears to have bone catabolic effects in boys and girls. This effect is mainly mediated by the negative association with total protein intake and is not primarily based on milk displacement.

Background: Observational studies in adults suggest that a diet with a high glycemic index (GI) or glycemic load (GL), a high intake of sugary foods, or a low fiber intake may increase the risk of overweight., Objectives: We aimed to examine prospectively whether dietary GI, GL, added sugar intake, or fiber intake between age 2 and 7 y are associated with the development of body composition. If so, we aimed to ascertain whether these associations are modified by meal frequency., Design: Linear mixed-effect regression analyses were performed in 380 participants of the DOrtmund Nutrition and Anthropometric Longitudinally Designed (DONALD) Study for whom 4-6 weighed 3-d dietary records and anthropometric data were obtained between ages 2 and 7 y., Results: Changes in dietary GI, GL, or added sugar intake between ages 2 and 7 y were not associated with concurrent changes in percentage body fat (%BF, as estimated from skinfold thicknesses) or body mass index SD scores. An increase in fiber intake was related to a concurrent decrease in %BF between ages 2 and 7 y only in children who consumed <6 meals/d as toddlers (beta +/- SE from fully adjusted model: -0.26 +/- 0.09%BF per 1-SD increase in fiber intake, P = 0.005), whereas children with a higher meal frequency had no concurrent change (0.07 +/- 0.07%BF per 1-SD increase in fiber intake, P = 0.3)., Conclusions: Dietary GI, GL, or added sugar intake between ages 2 and 7 y does not appear to influence the development of body composition. Potential benefits associated with increasing fiber intake throughout childhood may be limited to toddlers with a lower meal frequency.

Objectives: To evaluate whether renal net acid excretion capacity (NAEC) varies across different age groups and, specifically, whether it falls in elderly people., Design: Cross-sectional observational study., Setting: Community-based., Participants: Young participants were from the DOrtmund Nutritional and Anthropometric Longitudinally Designed Study, Dortmund, Germany; elderly participants were from Gothenburg, Sweden., Measurements: Twenty-four-hour urine pH, net acid excretion (NAE), urinary phosphorus, total nitrogen excretion, and anthropometric data were measured in healthy elderly people (aged 55-75; n=85), young adults (aged 18-22; n=117), adolescents (aged 13-14; n=112), and prepubescent children (aged 6-7; n=217). NAEC was determined as 24-hour NAE adjusted for urine pH using the residual method., Results: In elderly participants 24-hour urinary pH (5.9+/-0.53) was lower (P<.05) and NAE (60+/-27 mEq/d) higher (P<.05) than in the three other groups. In a regression model adjusted for age, sex, and body surface area, NAEC showed a clear decrease with age, with highest values in prepubescents and lowest in elderly participants. However, NAEC remained significantly lower only in elderly participants (P<.001) after the inclusion of total nitrogen excretion, a protein intake index, which was included because protein intake is known to modulate renal function. NAEC was approximately 8 mEq/d lower in healthy elderly participants than in young adults., Conclusion: The capacity to excrete net endogenous acid does not vary markedly from childhood to young adulthood but falls significantly with age, implying that elderly people may require higher daily alkalizing mineral intake to compensate for renal function losses.

The present study investigated whether subcutaneous fat differs in the impact on bone development from fat mass (FM). We analyzed 295 healthy children and adolescents (age 5-19 years, 139 males) for FM by measuring four skinfold thicknesses and for bone development and body composition at the forearm by peripheral quantitative computed tomography in a cross-sectional investigation. Relative cross-sectional fat area (FA) was a surrogate for relative subcutaneous FM at the forearm and was associated positively with percent fat in prepubertal individuals and pubertal females but negatively in pubertal males. Percent FM was associated with trabecular bone mineral density (BMDtrab) in prepubertal individuals (females r = 0.394, males r = 0.242) and pubertal individuals (females r = 0.215, males r = -0.275). Bone mineral count was correlated with percent FM in pubertal males (r = -0.287). FA was correlated with BMDtrab (r = 0.285) and with cortical bone mineral density (BMDcort, r = -0.296) in pubertal females. The ratio FA/ FM was negatively correlated with BMDcort (r = -0.299) in pubertal females. Pubertal females with relatively high subcutaneous fat area (high ratio FA/FM) were characterized by lower bone strength (P = 0.047). FM and the relative amount of subcutaneous fat have effects on bone formation and resorption that depend on gender and puberty. Especially in pubertal females, higher levels of subcutaneous fat may decrease bone strength due to increased cortical remodeling.

Objective: To investigate the effect of breastfeeding in healthy boys and girls on their trajectories of percent body fat (%BF) and BMI standard deviation scores (BMI-SDS) throughout childhood., Methods and Procedures: Analyses of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study included data from 219 male and 215 female term participants, born between 1984 and 1999, with repeated anthropometric measurements between 0.5 and 7 years and prospective data on duration of breastfeeding., Results: Among boys with an overweight mother (OW-M), analyses adjusted for potential confounders revealed that not or shortly breastfed (< or =17 weeks) boys did not experience the age-dependent decrease in %BF seen in all children with normal weight mothers (NW-Ms). In contrast, boys fully breastfed for >17 weeks were protected against the adverse effect of maternal overweight (effect of long breastfeeding vs. no/short breastfeeding among boys with OW-Ms: 0.46%/year; s.e. 0.18; P = 0.01). There was also a suggestion of an interaction between maternal overweight and breastfeeding for the BMI-SDS trajectory (0.08 SDS/year; s.e. 0.04; P = 0.07). Among boys with NW-Ms mothers and the corresponding subgroups of girls, breastfeeding had little effect on the development of %BF or BMI-SDS throughout childhood., Discussion: Our study suggests that breastfeeding could offset a potential programming effect for childhood adiposity among boys with OW-Ms, to whom advice to breast-feed should thus be specifically targeted.

Primarily experimental evidence suggests that endogenous glucocorticoids may be suppressed by adipocyte-derived leptin and elevated by dietary acidity. Therefore, we examined whether these factors may also be relevant in healthy adults on unrestricted diets. For this we used a new methodological approach in which potentially bioactive free glucocorticoids were determined as the sum of urinary free cortisol and urinary free cortisone and that also takes into account total adrenal glucocorticoid secretion assessed by the sum of the 3 major urinary glucocorticoid metabolites tetrahydrocortisone, tetrahydrocortisol, and 5alpha-tetrahydrocortisol. Body composition, plasma cortisol, plasma leptin, and 24-h urinary excretion rates of net acid and glucocorticoid metabolites were examined cross-sectionally in 30 healthy adults (15 women; 22-44 y old; BMI 20-25 kg/m2). Plasma leptin, percentage body fat, and body surface area-corrected adrenal glucocorticoid secretion showed the usual sex dimorphism (male vs. female, P < 0.05 in each case: 2.8 +/- 1.6 microg/L vs. 7.6 +/- 4.9 microg/L, 16.8 +/- 4.2% vs. 26.9 +/- 4.9%, and 5.1 +/- 1.6 mg x m(-2) x d(-1) vs. 4.0 +/- 1.3 mg x m(-2) x d(-1), respectively), whereas net acid excretion, plasma cortisol, and potentially bioactive free glucocorticoids did not differ between the sexes. Potentially bioactive free glucocorticoids correlated positively with body fat and leptin in men (P < 0.05) but not in women. After adjustment for total adrenal glucocorticoid secretion, net acid excretion was a positive and leptin a negative predictor (P < 0.05) of potentially bioactive free glucocorticoids in women only (total explained variability R2 = 0.71). Our findings indicate that, at least in women, variability of potentially bioactive free glucocorticoids is not only explained by adrenal glucocorticoid secretion but is also metabolically affected by circulating leptin and diet-dependent net acid excretion.

The role of nutrition in human acid-base homeostasis has gained increasing attention in recent years. Although in healthy humans, homeostatic mechanisms and the kidneys' capacity to excrete acid equivalents can prevent strong diet-induced alterations in blood pH, even moderate increases in blood hydrogen ion levels as a result of unfavorable diet composition can have long-term consequences for the occurrence and progression of a number of diseases. The Second International Acid-Base Symposium, Nutrition-Health-Disease, provided deeper insight and updates in the scientific basis of the relation among diet, acid-base homeostasis, physiology, and pathophysiological consequences.

For examination of glucocorticoid metabolism and identification of hyper and hypocortisolism, various measurements and diagnostic tools are available. After a brief overview of the physiology of glucocorticoid secretion and glucocorticoid actions, the currently used measurements for blood, saliva, and urine samples and the corresponding physiological and metabolic implications are critically reviewed. A special emphasis is placed on the potential of 24-h urine analyses to assess not only glucocorticoid secretion, but also functional glucocorticoid activity.

Background/aims: The present analyses intend to clarify if gender and puberty modify the relationship between bone development (modeling and remodeling) and fat mass at the forearm., Methods: Data were collected from participants (139 males, 157 females, age = 5-19 years) of the Dortmund Nutritional and Anthropometric Longitudinally Designed study in a cross-sectional investigation. The main outcome measures were total and trabecular bone mineral density (BMDtot and BMDtrab), strength strain index (SSI) and parameters associated with modeling (cortical area, CA; periosteal circumference, CP) and remodeling (cortical bone mineral density, BMDcort, endosteal circumference, CE) were analyzed in their relationship to cross-sectional fat (FA) and muscle area (MA) at the forearm., Results: BMDtot was correlated with FA in pubertal males (r = -0.25). BMDtrab was contrarily predicted by FA in pubertal males and females (r = -0.28 vs. 0.31). FA was correlated with BMDcort (r = -0.32) and CE (r = 0.26) in pubertal females. MA was positively correlated with CA, CP and SSI., Conclusions: Modeling and bone strength were primarily predicted by MA. Markers of remodeling were positively correlated with FA in pubertal females, but not in prepubertal individuals and pubertal males. Therefore, gender and puberty modify the relationship between FA and bone development., (Copyright 2008 S. Karger AG, Basel.)

Background: Several reports give evidence that the perichondral ossificiation of bone tubes (modeling) strongly depends on muscular forces in children and adolescents. The present analyses intend to investigate the hypothesis that muscular forces also partly determine enchondral ossification and, therefore, longitudinal growth of bone tubes., Subjects and Methods: Analyses were based on a single cross-sectional investigation with peripheral quantitative computed tomography in 296 individuals (age 5-19 years) participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study., Results: Forearm length (FL) was correlated with body height in gender-related subgroups of prepubertal and pubertal individuals (rs between 0.76 and 0.86). Cross-sectional muscle area (MA) increased faster than FL and faster than cross-sectional bone area (BA) close to the distal growth plate in puberty. Close to the growth plate, longitudinal growth was faster than perichondral ossification in females. The ratio MA/BA (surrogate of pressure on the distal growth plate) was correlated with FL in prepubertal boys (r = -0.249, p = 0.043) and pubertal individuals (r = 0.153, p = 0.051)., Conclusions: Results support the hypothesis that longitudinal growth precedes modeling at the distal forearm. Confounding variables such as puberty may modify the relationship between muscle forces and longitudinal growth at the forearm in boys., (Copyright 2008 S. Karger AG, Basel.)

Background: Cross-sectional fat area (FA) and muscle area have been recently used to describe local body composition at the forearm in children and adolescents. The present analysis intends to characterize FA in a normal collective., Methods: FA was measured by peripheral quantitative computed tomography in a study collective (DONALD study) of 296 children and adolescents. FA was analyzed in relation to fat mass (FM) measured by 4 skinfold thicknesses., Results: FA was significantly correlated with FM (r = 0.8). FA was positively associated with height in prepubertal individuals and pubertal females, but negatively associated with height in pubertal males. Median and range of FA are displayed for different height ranges and pubertal stages in males and females to enable analyses of FA in subgroups., Conclusion: Because of the positive dependence of FA on height in prepubertal individuals and pubertal females, reference values of FA may be based on height. But reference values in pubertal males or in a mixed pubertal population should be rather based on pubertal stages than on height., ((c) 2008 S. Karger AG, Basel)

Background: Experimental studies have reported that the effect of a meal's glycemic index (GI) on subsequent energy intake depends on the timing of the subsequent meal., Objective: We examined whether the timing of the next meal after breakfast modifies the effect of the breakfast GI (GI(br)) on subsequent daytime energy intake of healthy free-living children., Design: Analyses included 381 participants of the DOrtmund Nutritional and Anthropometrical Longitudinally Designed (DONALD) Study who had provided weighed dietary records at ages 2, 4-5, and 7 y., Results: At all ages, among children who consumed their next meal in the early postprandial phase (after 3-4 h), children with a lower GI(br) consumed more calories throughout the remainder of the day than did children with a higher GI(br), independent of major dietary confounders. For the age groups 2, 4-5, and 7 y, energy intakes in tertiles 1 and 3 were 785 kcal (95% CI: 743-830 kcal) and 717 kcal (678-758 kcal), P for trend = 0.2; 993 kcal (941-1047 kcal) and 949 kcal (900-1000 kcal), P for trend = 0.05; 1255 (1171-1344) and 1166 (1090-1247 kcal), P for trend = 0.03, respectively. Conversely, among children consuming their next meal in the late postprandial phase (>3-4 h), subsequent daytime energy intake was not associated with GI(br)., Conclusion: This study confirms differential early and late postprandial effects of the GI(br) on subsequent daytime energy intake for free-living children at different ages. Interestingly, the apparent short-term satiating effect of a higher GI(br), in particular, persisted throughout the day, if a second breakfast was consumed midmorning.

Detailed data on the physiological pattern of adrenocortical activity during normal growth are lacking. An established method to determine adrenocortical glucocorticoid secretion is the measurement of 24-h excretion rates of major urinary cortisol metabolites (C21). To test the hypothesis that the frequently reported higher cortisol secretion in men than in women develops during puberty, we examined C21 together with excretions of combined urinary free and conjugated cortisol (F(comb)) in 400 healthy boys and girls aged 3-18 yr using GC-MS. Daily excretion rates of C21, F(comb), and body surface area (BSA)-corrected F(comb) significantly increased with age in both sexes. In contrast, C21/BSA (microgxm(-2).day(-1)) declined from the age of 3-4 yr to 7-8 yr in boys and girls (P < 0.01; e.g., in boys: from 3,991 +/- 1,167 to 3,193 +/- 804), then increased in both sexes, and finally became discordant after the age of 11-12 yr with a further rise in males only (17- to 18-yr-olds: boys, 5,275 +/- 1,414; girls 3,939 +/- 1,586, P < 0.01). This pattern was associated with the occurrence of a lower index for 5alpha-reductase activity (allotetrahydrocortisol/tetrahydrocortisol) in females compared with males. Our results demonstrate dynamic changes in adrenocortical activity in healthy children resulting in an emerging sexual dimorphism in cortisol secretion after age 11. The latter can be explained, at least partly, by diverging 5alpha-reductase activities in boys and girls. F(comb), a frequently analyzed GC-MS parameter, proved not to reflect dynamic changes in cortisol secretion. In conclusion, the varying metabolic need for cortisol during normal growth may have implications for future improvements in glucocorticoid replacement therapy.

Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing's syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1) regenerates active cortisol from inactive cortisone. Altered 11beta-HSD1 may cause tissue-specific Cushing's syndrome with central obesity and impaired glucose homeostasis., Design, Patients, and Methods: Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male and 6 female obese pubertal children (aged 12-18 years, Tanner stages 2-5). In addition, analyses of 24-h excretion rates of glucocorticoids were also performed in 21 age-, sex-, and pubertal stage-matched non-obese children using gas chromatographic-mass spectrometric (GC-MS) analysis., Results: 11beta-HSD1 activity (urinary tetrahydrocortisol (THF) + 5alpha-THF/tetrahydrocortisone (THE) ratio) was lower in obese when compared with non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11beta-HSD1 activity was significantly related to age in lean and obese children. Standard deviation score (SDS)-body mass index did not correlate with 11beta-HSD1 activity, or with total cortisol metabolite excretion within each group. In obese children, 11beta-HSD1 activity and total cortisol metabolite excretion showed no correlation to waist-to-hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index., Conclusions: In conclusion, our findings strongly suggest that 11beta-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children have a higher total cortisol metabolites excretion suggesting a stimulated hypothalamus-pituitary-adrenal axis.

Objective: In patients with nephrolithiasis, an inverse relationship between 24-h urinary pH (24h-UpH) and body weight has been reported. Whether body composition indices and 24h-UpH are similarly associated in healthy subjects needs investigation., Design: Cross-sectional, retrospective analysis., Setting: Dortmund, Germany and Gothenburg, Sweden., Subjects: Healthy young adults (18-23 years; n=117) and elderly (55-75 years; n=85) having a mean body mass index (BMI) of 22.80+/-3.4 and 25.3+/-3.9 kg/m2, respectively., Methods: Anthropometric data, 24h-UpH, and 24-h urinary excretion rates of net acid (NAE), creatinine, and urea were determined. After adjusting for urea (reflecting protein intake), renal creatinine output was used as a biochemical marker for muscularity. The BMI served as a marker of adiposity., Results: NAE, body weight, and BMI were significantly (P<0.05) higher, and height and creatinine significantly lower in the elderly, whereas body-surface area (BSA) was not different. Step-wise multiple regression analysis using BSA-corrected urinary variables revealed NAE as the primary predictor of 24h-UpH (with R2 values of 0.64 and 0.68 in young adults and elderly, respectively, P<0.0001), followed by urea (P<0.0001), creatinine (P<0.05), and BMI (P<0.05 for the young adults and P=0.12 for the elderly). These associations were negative for NAE and BMI, and positive for urea and creatinine., Conclusions: Muscularity (i.e. creatinine adjusted for urea) and particularly in the group of young adults, adiposity (i.e. BMI) proved to be modest, but significant predictors of 24h-UpH. Future research should focus on more obese subjects in whom insulin resistance and particular kidney functions should also be examined to further substantiate the role of obesity in low-urine pH-associated conditions, for example, nephrolithiasis.

Magnesium and calcium deficiency in humans is related to a number of pathological phenomena such as arrhythmia, osteoporosis, migraine, and fatal myocardial infarction. Clinically established metabolic acidosis induces renal losses of calcium. In normal subjects, even moderate increases in net endogenous acid production (NEAP) impair renal calcium reabsorption but no information is available whether this also influences renal magnesium handling. The aim of the study was to examine the relation between NEAP and renal magnesium excretion in healthy, free-living, elderly subjects. The subjects (age 64 +/- 4.7 y, n = 85) were randomly selected from the population register in Gothenburg (Sweden). Magnesium, calcium, and potassium were measured in 24-h urine samples and NEAP was quantified as renal net acid excretion (NAE). NAE was positively correlated with excretions of magnesium (R(2) = 0.27, P < 0.0001) and calcium (R(2) = 0.30, P < 0.0001) but not potassium. When 24-h urinary magnesium excretion was adjusted for 24-h urinary potassium excretion, a biomarker for dietary potassium intake, the association between magnesium excretion and NAE remained significant (R(2) = 0.21, P < 0.0001). The significant association between potassium-adjusted magnesiuria and NAE suggests that the acid-base status affects renal magnesium losses, irrespectively of magnesium intake. Magnesium deficiency could thus, apart from an insufficient intake, partly be caused by the acid load in the body.

Reported literature data strongly suggest that steroid metabolism is dysregulated in Type 1 diabetes mellitus. The aim of this study was to non-invasively examine the cortisol metabolism in children with Type 1 diabetes mellitus (T1DM) in detail and to test the hypothesis that adrenarche is affected under conventional intensive insulin therapy. In 24-h urine samples of 109 patients aged 4-18 years with T1DM of more than 1 year, steroids were profiled using gas chromatography-mass spectrometry. Additionally, urinary free cortisol (UFF) and cortisone (UFE) were quantified by RIA after extraction and chromatographic purification. Data on urinary steroids from 400 healthy controls served as reference values. Enzyme activities were assessed by established steroid metabolite ratios, e.g. 5alpha-reductase and 11beta-hydroxysteroid dehydrogenase Type 2 (11beta-HSD2) by 5alpha-tetrahydrocortisol/tetrahydrocortisol and UFE/UFF, respectively. Urinary markers of adrenarche, especially dehydroepiandrosterone and its direct metabolites were elevated in patients, as were urinary 6beta-hydroxycortisol, UFE, and 11beta-HSD2 activity. However, overall cortisol secretion, as reflected by the sum of major urinary cortisol metabolites, was mostly normal and activity of 5alpha-reductase clearly reduced. Our study provides evidence for an exaggerated adrenarche in T1DM children, which may help to understand reported sequelae in female patients like hyperandrogenic symptoms. The findings also suggest a reduced cortisol inactivation via 5alpha-reductase that is not compensated by a fall in cortisol secretion. Whether the elevated urinary 6beta-hydroxycortisol and cortisone excretion, observed in the patients, are also present in other forms of hypercortisolism and may thus serve as non-invasive clinical stress markers deserves further study.

This study first examined whether urinary C-peptide (UCP), stored at -20 degrees C, remains stable over the long term, and second, whether the dietary glycemic index (GI) and the glycemic load (GL: GI x g carbohydrates) are related to the 24-h UCP excretion of healthy children. Participants in the Dortmund Nutrition and Anthropometric Longitudinally Designed Study with 24-h urine collections and a simultaneously completed weighed dietary record were included. From these, 3 comparable groups of 7- to 8-y-old children (n = 40 each) from 1990, 1996, and 2002 were randomly selected (total n = 120). C-peptide was measured with a 1-site ELISA. A GI value was assigned to all recorded foods containing carbohydrates (CHO). Statistical equivalence tests corroborated that UCP excretion in the 3 sampling periods was equivalent when corrected for body weight and protein intake (P < 0.05). UCP excretion was associated with the GL after adjustment for body weight, protein, and fiber intake [mean UCP (95% CI) in GL tertiles 1-3: 6.19 (5.37, 7.14) vs. 7.82 (6.77, 9.02) vs. 7.76 (6.71, 8.97) nmol/d, P for difference 0.04]. GI was not significantly related to UCP excretion [adjusted means (95% CI): 7.27 (6.28, 8.41) vs. 6.51 (5.64, 7.51) vs. 7.94 (6.86, 9.18), P for difference 0.2]. In conclusion, UCP retrospectively measured with a 1-site ELISA remained stable for up to 12 y (from 1990 until 2002). The observed positive relation of UCP with GL appears to result largely from its association with the amount of CHO, whereas dietary GI may be relevant only at higher intake levels.

The role of elevated net endogenous acid production (NEAP) in the causation of osteoporosis, muscle wasting, and kidney stones is currently under discussion. The aim of this study was to examine whether urinary organic acid anion excretion, a major component of NEAP, is predicted primarily by anthropometric- (OA(anthro)) or diet- (OA(diet)) based estimates. Dietary intakes, anthropometric data, and 24-h urinary excretion rates of organic acids (24h-OA(urine)) were determined cross sectionally in healthy children (6-7 y; n = 217), adolescents (13-14 y; n = 91), and young adults (18-22 y; n = 82). OA(anthro) was computed from body surface area and OA(diet) calculated using a published algorithm based on dietary intakes of mineral anions and cations. There was a significant increase (P < 0.0001) in 24h-OA(urine) across the age groups that was no longer discernible after correction for body surface area. In almost all sex-stratified subsamples, OA(anthro) had a higher correlation with 24h-OA(urine) than OA(diet). Multiple regression analyses, using energy-corrected diet variables, revealed that OA(anthro) was consistently the primary predictor of 24h-OA(urine) (R(2) varying from 0.15 to 0.39) and dietary fat and protein were sporadic predictors. In accordance with the observed age independency of 24h-OA(urine) after body surface area correction, our findings indicate that OA(anthro) is a better estimate of 24h-OA(urine) in healthy children, adolescents, and young adults than OA(diet). This further confirms that the (principally diet-dependent) NEAP comprises a component, i.e., organic acid anions, that is reasonably predictable by anthropometrics. Consequently, the other component, i.e., the potential renal acid load, appears to be the primary parameter that characterizes the diet-induced acid load.

Background: Because worldwide iodine status (IS) depends on continuous fortification, the adequacy of IS needs to be regularly monitored., Objective: Our study aimed to evaluate IS in a longitudinal sample of healthy schoolchildren who regularly used table salt iodized with 20 microg I/g., Design: Urine osmolality (Uosm) and 24-h urinary excretion rates of iodine (24-h UI), sodium, creatinine, and total urine volume (24-h Uvol) were measured in 1046 specimens that were collected at repeated intervals from 1996 to 2003 in a sample of 358 German children aged 6-12 y. Energy intake and food consumption were calculated from 3-d weighed dietary records that were collected in parallel to the urine samples., Results: During the 4-y period from 1996 to 1999, the median 24-h UI increased from 87 to 93 microg I/d (P = 0.017), whereas urinary iodine concentration (UIC), Uosm, and 24-h Uvol did not change significantly. Thereafter (from 2000 to 2003), UIC stagnated and Uosm decreased (P = 0.004), whereas 24-h Uvol (P = 0.008) and 24-h UI (P = 0.002) increased. The final median 24-h UI reached 120 microg I/d. Milk, fish, egg, and meat intakes and 24-h sodium excretion were all significant predictors of IS, with an almost doubled contribution from milk intake during the second 4-y period., Conclusions: Our study shows a continuous improvement of IS in a longitudinal sample of German schoolchildren. This improvement was masked when UIC was used as an IS index, especially from 2000 to 2003 because of changes in hydration status. Thus, in research-oriented studies that focus on UIC measurements, hydration status can be a relevant confounder. Longitudinal analyses of 24-h UI in cohort studies may represent an alternative hydration status-independent tool to examine trends in IS and the contribution of relevant foods to IS.

Background: Protein and alkalizing minerals are increasingly described as playing a major role in influencing bone status, not only in the elderly but also in children and adolescents., Objective: We examined whether the long-term dietary protein intake and diet net acid load are associated with bone status in children., Design: In a prospective study design in 229 healthy children and adolescents aged 6-18 y, long-term dietary intakes were calculated from 3-d weighed dietary records that were collected yearly over the 4-y period before a one-time bone analysis. Dietary acid load was characterized as potential renal acid load (PRAL) by using an algorithm including dietary protein, phosphorus, magnesium, and potassium. Proximal forearm bone variables were measured by peripheral quantitative computed tomography., Results: After adjustment for age, sex, and energy intake and control for forearm muscularity, BMI, growth velocity, and pubertal development, we observed that long-term dietary protein intake was significantly positively associated with periosteal circumference (P < 0.01), which reflected bone modeling, and with cortical area (P < 0.001), bone mineral content (P < 0.01), and polar strength strain index (P < 0.0001), which reflected a combination of modeling and remodeling. Children with a higher dietary PRAL had significantly less cortical area (P < 0.05) and bone mineral content (P < 0.01). Long-term calcium intake had no significant effect on any bone variable., Conclusions: Long-term dietary protein intake appears to act anabolically on diaphyseal bone strength during growth, and this may be negated, at least partly, if dietary PRAL is high, ie, if the intake of alkalizing minerals is low.

Information on the urinary excretion of dehydroepiandrosterone (DHEA) and its direct metabolites is scarce for healthy subjects during growth. We used gas chromatography-mass spectrometry urinary steroid profiling to noninvasively study adrenarchal metabolome in 400 healthy subjects, aged 3-18 yr. Urinary 24-h excretion rates of DHEA did not increase significantly before age 7-8 yr. However, DHEA together with its 16alpha-hydroxylated downstream metabolites, 16alpha-hydroxy-DHEA and 3beta,16alpha,17beta-androstenetriol (DHEA&M), as well as the DHEA metabolite, 5-androstene-3beta,17beta-diol (ADIOL), and the sum of major urinary androgen metabolites (C19) rose consistently from the youngest to the oldest age group. The significant increases (P < 0.01) observed for 24-h excretion rates of C19, ADIOL, and DHEA&M were 2- to 4-fold in boys and girls between age 3 and 8 yr. DHEA&M, for example, rose from about 20 to 80 microg/d (P < 0.0001) during this period. Until the age of 16 yr, DHEA&M excretion also increased to nearly 1000 microg/d. Patterns of steroidogenic enzyme activities were assessed (from definite ratios of urinary steroid metabolites) for 21-hydroxylase, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, and 5alpha-reductase. Our results indicate for healthy boys and girls that adrenarche is a gradual process starting much earlier than hitherto believed. Efficient metabolism of DHEA, especially to 16-hydroxylated steroids, may explain the almost constant levels seen for this steroid until age 7-8 yr. The established reference values for DHEA, DHEA&M, ADIOL, C19 (including androsterone and etiocholanolone), and urinary parameters of steroidogenic enzyme activities could be useful to identify nutritional, environmental, and pathophysiological interrelations with the progressive maturational process of adrenarche. Our data may also be used as reference data for the diagnosis of steroid-related disorders.

Bone densitometry is currently one of the mainstays in the evaluation of systemic bone diseases in adults and is also increasingly used to assess primary or secondary bone disorders in children and adolescents. The purpose of carrying out densitometric studies in such circumstances is to measure the densitometric indicators of bone stability. Following procedures which were established for diagnosing adult osteoporosis, a decrease in densitometric surrogates of bone stability is usually interpreted as indicating increased fracture risk. The most basic densitometric parameter is bone mineral content (BMC), which can be measured with most densitometric techniques. BMC is either defined as the mass of mineral contained in an entire bone or as the mass of mineral per unit bone length. While mineral mass can be expected to be a good surrogate for bone stability, BMC is obviously a size-dependent parameter, since small bones weigh less than big bones. This is a drawback in paediatric use, since many children and adolescents who are examined by densitometry suffer from chronic disorders and are small-for-age. Short children will have a lower BMC than their healthy age-matched peers, even if their (smaller) bones are otherwise completely normal.

Nutrition during childhood and adolescence is an important determinant of development and health, both for the child and the later adult. In industrialised countries as well as in many countries of economic transition, emphasis has moved from combating nutrient deficiencies to research on the effects of overnutrition and food selection. Prevention of chronic diseases including obesity have become a major focus in research. However, the complex relation between infant growth and its related endocrine and metabolic changes on the one hand and the influence of nutrition and nutritional status on the other hand still need to be understood in detail. Studies aiming to elucidate this have to follow children and adolescents during their growth period. The following pages display the features of the German DONALD Study ( DOrtmund Nutritional and Anthropometric Longitudinally Designed Study) which was specifically designed to address these complex research questions. Finally, comparisons to other studies are made and the specific strength and weaknesses of this study are discussed. As the DONALD study offers unique research opportunities and due to its long follow-up an abundance of data, collaborative research is encouraged.

Hypotheses: A cross-sectional study on urinary excretion of 6-sulfatoxymelatonin (aMT.6S) in young adults suggests a relation between melatonin production and body size at birth. As individual melatonin production remains stable during childhood and adolescence, this melatonin-birth size relation should also exist in children., Methods: Daily urinary output of aMT.6S of 147 healthy white children (78 boys, 69 girls), 8 or 9 years of age, was quantified by ELISA and related to birth variable data., Results: Contrary to expectation, aMT.6S output was not related to the ponderal index at birth but a moderate positive association with body mass index at the age of 8-9 years was seen., Conclusion: This study in children contradicts previous findings in adults. As no obvious reason can be identified for this discrepancy, further research (particularly a longitudinal study) is recommended to clarify whether birth variable data may predict melatonin production in certain circumstances during or after puberty., (2004 S. Karger AG, Basel)

Background/objectives: The responses of metaphyseal bone tissue to physiological variations of endogenous adrenal steroid hormones during childhood are unclear. Therefore, we studied potential hormonal influences in children before the appearance of pubic hair (onset of pubarche)., Methods: Excretions of major glucocorticoid metabolites (C21), cortisol, sum of adrenarchal dehydroepiandrosterone and its immediate 16-hydroxylated metabolites (DHEA&M), and 5-androstene-3beta,17beta-diol (hermaphrodiol) were analyzed in a cross-sectional study in 24-hour urine samples of 109 healthy boys and girls, aged 6-13 years, using steroid profiling by gas chromatography-mass spectrometry. Total and trabecular volumetric bone mineral densities, bone mineral content (BMC) and bone strength strain index were determined with peripheral quantitative computed tomography at the distal forearm., Results: In multiple regression analyses significant associations with the metaphyseal radius were seen for grip force, age, or BMI depending on gender and bone variable analyzed. DHEA&M did not contribute to the explanation of the variance of any bone variable. However, hermaphrodiol positively explained a significant part of variation of bone mineral densities, and BMC (p < 0.01) in girls. Significantly negative associations with all bone variables were seen in boys for cortisol., Conclusions: The steroid hormones, cortisol and hermaphrodiol, in their physiological ranges, but not the adrenarche marker DHEA&M, appear to associate with metaphyseal bone in a sex-dependent manner during childhood., (Copyright (c) 2004 S. Karger AG, Basel.)

The analysis was performed to support the assumption that in inter-individual variations melatonin production is determined genetically. Sixty-six siblings from 31 families (27 girls, 39 boys, 3-18 years) contributed to this study with 3 to 15 urine samples collected once a year over 24 h. The samples were stored at -20 degrees C and analyzed for the daily output of the melatonin metabolite 6-hydroxymelatonin sulfate (6-OHMS) by an enzyme-linked immunosorbent assay (ELISA). The results indicate that 6-OHMS excretion was significantly correlated in siblings (r = 0.37, p = 0.01), suggesting a possible genetic background of melatonin production. However, prospective studies controlling also lifestyle factors such as diet are required to further confirm the hypothesis., (Copyright 2003 S. Karger AG, Basel)

Unlabelled: Adrenarche, the physiological increase in adrenal androgen secretion, may contribute to better bone status. Proximal radial bone and 24-h urinary steroid hormones were analyzed cross-sectionally in 205 healthy children and adolescents. Positive adrenarchal effects on radial diaphyseal bone were observed. Obviously, adrenarche is one determinant of bone mineral status in children., Introduction: Increased bone mass has been reported in several conditions with supraphysiological adrenal androgen secretion during growth. However, no data are available for normal children. Therefore, our aim was to examine whether adrenal androgens within their physiological ranges may be involved in the strengthening of diaphyseal bone during growth., Methods: Periosteal circumference (PC), cortical density, cortical area, bone mineral content, bone strength strain index (SSI), and forearm cross-sectional muscle area were determined with peripheral quantitative computed tomography (pQCT) at the proximal radial diaphysis in healthy children and adolescents. All subjects, aged 6-18 years, who collected a 24-h urine sample around the time of their pQCT analysis (100 boys, 105 girls), were included in the present study, and major urinary glucocorticoid (C21) and androgen (C19) metabolites were quantified using gas chromatography-mass spectrometry., Results and Conclusions: We found a significant influence of muscularity, but not of hormones, on periosteal modeling (PC) before the appearance of pubic hair (prepubarche). Similarly, no influence of total cortisol secretion (C21) was seen on the other bone variables. However, positive effects of C19 on cortical density (p < 0.01), cortical area (p < 0.001), bone mineral content (p < 0.001), and SSI (p < 0.001)--reflecting, at least in part, reduction in intracortical remodeling-were observed in prepubarchal children after muscularity or age had been adjusted for. This early adrenarchal contribution to proximal radial diaphyseal bone strength was further confirmed for all cortical variables (except PC) when, instead of C19 and C21, specific dehydroepiandrosterone metabolites were included as independent variables in the multiple regression model. During development of pubic hair (pubarche), muscularity and pubertal stage rather than adrenarchal hormones seemed to influence bone variables. Our study shows that especially the prepubarchal increase in adrenal androgen secretion plays an independent role in the accretion of proximal radial diaphyseal bone strength in healthy children.

Background: There is increasing evidence that acid-base status has a significant effect on high-intensity physical performance, urolithiasis, and calcium metabolism. Experimental studies in adults showed that renal net acid excretion (NAE) can be reliably estimated from the composition of diets., Objective: We investigated whether a reasonable estimation of NAE is also possible from the dietary records of free-living children and adolescents., Design: Healthy children (aged 8 y; n = 165) and adolescents (aged 16-18 y; n = 73) each collected a 24-h urine sample and completed a weighed diet record on the same day. Urinary NAE was analyzed (NAE(an)) and estimated (NAE(es)). Potential renal acid load (PRAL), the diet-based component of NAE(es), corrects for intestinal absorption of ingested minerals and sulfur-containing protein. A urinary excretion rate of organic acids (OAs) proportional to body surface area was assumed for the complete estimate (NAE(es) = PRAL + OA(es))., Results: Significant (P < 0.001) correlations between NAE(es) and NAE(an) were seen in the children (r = 0.43) and the adolescents (r = 0.51). A simplified estimate based on only 4 components of dietary PRAL (protein, phosphorus, potassium, and magnesium) yielded almost identical associations. Mean simplified NAE(es) (32.6 +/- 13.9 and 58.4 +/- 22.0 mEq/d in the children and the adolescents, respectively) agreed reasonably with NAE(an) (32.4 +/- 15.5 and 52.8 +/- 24.3 mEq/d, respectively)., Conclusions: Predicting NAE from dietary intakes, food tables, and anthropometric data is also applicable during growth and yields appropriate estimates even when self-selected diets are consumed. The PRAL estimate based on only 4 nutrients may allow relatively simple assessment of the acidity of foods and diets.

Background: Excess endogenous or exogenous cortisol is a potent stimulus for fat gain., Objective: We examined whether physiologic variations in endogenous cortisol secretion may be associated with changes in body composition during growth., Design: Anthropometric measurements and 24-h excretion rates of urinary free cortisol (UFF) and cortisone (UFE) and the sum of 3 major glucocorticoid metabolites (GC), which reflects overall daily cortisol secretion, were determined cross-sectionally in healthy preschool (50 boys and 50 girls aged 4-5 y), late prepubertal (50 boys and 50 girls aged 8-9 y), and pubertal (50 males aged 13-14 y and 50 females aged 12-13 y) subjects., Results: Significant positive associations (P < 0.001) were found between GC excretion and fat mass, percentage body fat, and body mass index by using covariance analysis adjusted for the grouping factors sex and age. The relations between GC and indexes of body fat remained significant (P < 0.05) even after GC was corrected for individual body surface area and the effect of maternal body mass index on fatness was considered. No consistent associations with fat indexes were seen for UFF, UFE, or the ratio of major urinary cortisol to cortisone metabolites, which reflects 11 beta-hydroxysteroid dehydrogenase type 1 activity., Conclusions: Although direct effects of UFF and UFE on body composition were not shown, our findings strongly suggest that a higher adrenocortical activity is one endocrine-metabolic feature of healthy children with higher body fat. Whether urinary GC is a long-term predictor of fat gain during childhood should be analyzed in future studies.

Cross-sectional data on urinary 6-hydroxymelatonin sulfate (6-OHMS) excretion in children suggest a constant melatonin secretion during growth. The present longitudinal study concerned, accordingly, the intra-individual stability of melatonin production during childhood and adolescence. Urine samples collected during a longitudinal investigation of healthy white children and adolescents were analyzed. Forty-six boys and 38 girls were chosen for the present study. They had passed 3-15 annual examinations between their 3rd and 18th yr of age. Each examination included the collection of urine over 24 hr. The daily urinary output of 6-OHMS of the overall 621 samples was quantified by enzyme-linked immunosorbent assay. The analyses clearly revealed for the first time that, despite huge inter-individual differences, melatonin production remains constant in one and the same individual during childhood and adolescence. Additionally, neither a significant sex difference was observed nor was the 6-OHMS output affected by season. The dramatic decrease of plasma melatonin levels as described in the literature is mainly related to an increase in body size rather than to decreasing pineal secretion.

Background: Anthropometric measurements are widely used to determine body composition, especially in children., Objective: Our aim was to compare 2 of the simplest anthropometry-based equations available for determining nutritional status and muscularity in children and adolescents, examined in relation to other methodologically independent muscle variables., Design: Midupper arm muscle area (UAMA) and fat-free mass (FFM) according to the equations of Slaughter et al (Hum Biol 1988;60:709-23), as well as separate biochemical, physical, and radiologic muscle variables, were determined cross-sectionally in 91 males and 91 females aged 6-18 y. The ability of UAMA and FFM to estimate muscularity, as measured by 24-h creatinine excretion, grip force, and peripheral quantitative computer tomography analysis of forearm muscle, was compared after dividing the study population into prepubertal and pubertal groups., Results: Before puberty, correlations of all 3 muscularity variables were higher with FFM than with UAMA in both males and females. Multiple regression analyses confirmed FFM to be the predominant predictor, with partial R(2) >/= 0.68 (P < 0.001). However, in puberty, FFM did not consistently show this major influence. Only before puberty did FFM provide a significantly better fit (P < 0.05) than did UAMA for 2 of the 3 muscularity variables in each sex., Conclusions: The FFM estimate proved to be the better predictor for muscularity in healthy prepubertal children and is on a par with UAMA during puberty. FFM can be recommended as a simple anthropometric method to assess nutritional status before puberty, at least in healthy children.

Background: Urinary creatinine reference values that take anthropometric data into account, which is mandatory during growth, are not available for healthy white children., Objective: We sought to establish anthropometry-based reference values for 24-h urinary creatinine excretion in healthy white children aged 3-18 y., Design: Anthropometric variables and 24-h urinary creatinine excretion rates were determined cross-sectionally (225 boys and 229 girls). Age and sex dependency of 24-h creatinine excretion (crude and related to individual anthropometric variables) were assessed to derive appropriate creatinine reference values. The applicability of these creatinine reference values for estimation of daily excretion of certain analytes was assessed in 40 additional children., Results: Sex-specific, body-weight-related creatinine reference values were derived for the following age groups: 3, 4-5, 6-8, 9-13, and 14-18 y. The 5th percentile exceeded 0.1 mmol x kg(-1) x d(-1) in all age groups >3 y. The use of these creatinine reference values for estimating average 24-h excretion rates of certain analytes (determined as the ratio of analyte to creatinine in spot urine samples) yielded reasonable estimates of mean 24-h urinary excretion rates actually analyzed (spot and 24-h urine samples from the same children). Ideal 24-h creatinine excretion values for height were also derived for a potential determination of the creatinine height index., Conclusions: Established anthropometry-based creatinine reference values are recommended as a convenient, simple tool to 1) identify severe 24-h urine collection errors, 2) calculate average 24-h excretion rates of certain analytes (from respective ratios of analyte to creatinine) determined in spot urine samples, and 3) assess somatic protein status by determining the creatinine height index.

Background: In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. The aim of this study was to assess the relationship of the urinary collagen markers deoxypyridinoline (DPD) and hydroxylysine (Hyl) and its glycosides [galactosyl-Hyl (Gal-Hyl) and glucosyl-Gal-Hyl] with growth., Methods: Urine samples from 240 apparently healthy children and adolescents (6-19 years; 124 girls) and from 51 prepubertal children with growth hormone (GH) deficiency (3-14 years; 14 girls) were analyzed. Urinary Hyl and its glycosides were quantified by HPLC, and DPD was assessed by chemiluminescence assay. Urinary concentrations of all markers were related to urinary creatinine., Results: Multiple regression analysis revealed that only age and height velocity were independently associated with these markers in healthy children. In GH-deficient patients, the urinary excretion of both analytes after 4 weeks of GH therapy correlated significantly with the height increase during the first treatment year (r = 0.79 for Gal-Hyl; r = 0.70 for DPD; P <0.001 each). In a multivariate linear regression model using Gal-Hyl concentrations at 4 weeks, baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 80% of the variability in height gain during the first treatment year. A model using DPD concentrations at 4 weeks, in place of Gal-Hyl concentrations, as well as baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 83% of the variability., Conclusions: These urinary bone and collagen markers give some early indication of growth response, but the prediction of an individual marker is too imprecise to serve as a basis for clinical decisions. Markers of bone and collagen metabolism might be more useful as components of multivariate growth prediction models.

Background: Nutrition has long been known to strongly influence acid-base balance. Recently, we have shown that it is possible to appropriately estimate the renal net acid excretion (NAE) of healthy subjects from the composition of their diets., Aim of the Study: 1) To briefly present a physiologically based calculation model that allows a reasonable estimation of the analytically determined urinary NAE, 2) to summarize the underlying metabolic mechanisms and 3) to study the specific effect of protein on ammoniagenesis which may counteract, to a small degree, the primary acid load-increasing potential of protein., Methods: The calculation model and the algorithm for predicting the dietary acid load are summarized, major metabolic (and intestinal) pathways of acid and base equivalents are explained, and urinary excretion rates of ammonium and NAE were specifically examined with special regard to the respective protein intake levels. For the latter examinations, data from diet experiments in adults and epidemiological data from children (protein intake; NAE, pH, and ammonium excretion in 24-h urine samples) were analyzed., Results: The paper shows that the diet-induced generation of acidity and alkalinity is not only determined by the metabolism (oxidation) of sulfur-containing amino acids and organic acid anions of alkali salts, respectively. The intestine is also directly involved in the generation of food-derived acid or alkali loads which is due to the considerably different intestinal absorption rates of relevant food components, i. e., protein and minerals. Further analyses of the interrelation between diet and acid-base status revealed that increasing protein intake (despite its potential to increase NAE) also significantly improves the capacity for renal net acid excretion by stimulating urinary ammonium excretion., Conclusion: An adequate concept to estimate renal NAE and potential renal acid loads from dietary intakes must consider the specific bioavailability of the individual nutrients. Furthermore, an increased protein intake does not necessarily result in an accordingly increased use of endogenous acid excretion capacity for two reasons: 1) additional alkali loads in an appropriately composed diet can compensate for the protein-related raised acid production and 2) protein itself moderately improves the renal capacity to excrete net acid by increasing the endogenous supply of ammonia which is the major urinary hydrogen ion acceptor.

A small transient increase in growth, the midgrowth spurt, has been observed in several growth studies in healthy children around the age of 7 yr. During this time adrenarche (the physiological increase in adrenal androgen secretion) also occurs. Although it is now well established that estrogen, not androgen, has a critical role in the male (and female) pubertal growth spurt, a direct effect of androgens on growth cannot be excluded. In accordance with published observations that growth is frequently accelerated in infants and young children with late-diagnosed 21-hydroxylase deficiency (before adequate androgen suppression), it has been speculated that the adrenarchal increase in adrenal androgen secretion in healthy children could be responsible for the midgrowth spurt. To test this hypothesis we studied long-term serial changes in urinary 24-h excretion rates of dehydroepiandrosterone sulfate and total 17-ketosteroid sulfates in a group of healthy children (n = 12) in which yearly auxological measurements allowed the identification of a midgrowth spurt. Annual measurements of standing height were performed over periods of 6-9 yr before the onset of puberty. All children collected five to seven serial 24-h urine samples (1-yr intervals) each at the time of anthropometric examination. The peak of the midgrowth spurt was found to occur at a mean age of 6.8 +/- 1.0 yr. The average height of the midgrowth peak, i.e. average maximum gain in height velocity, was 0.9 cm/yr. In a peak-centered examination of individual 24-h excretion rates of dehydroepiandrosterone sulfate and 17-ketosteroid sulfates, primarily weak 1-yr changes in adrenal androgens were observed until the peak was attained. Only after the peak did increments in urinary adrenal androgen output become more pronounced. ANOVA performed on the peak-centered dehydroepiandrosterone sulfate and 17-ketosteroid sulfate excretion rates revealed a highly significant overall increase in adrenal androgen secretion from 2 yr before to 2 yr after the midgrowth spurt. After multiple testing, however, significant increments, when compared with the respective preceding androgen excretion levels, were for the first time seen 1 yr after the midgrowth spurt (dehydroepiandrosterone sulfate) or 2 yr later (17-ketosteroid sulfates). In conclusion, our longitudinal analysis of prepubertal growth and urinary adrenal androgen excretion in healthy children disproves the speculation that the midgrowth spurt is primarily caused by the adrenarchal increase in adrenal androgen secretion. However, the present results do not rule out a growth-accelerating effect of clearly higher androgen levels, as in premature adrenarche.

The purpose of the present feasibility study was to determine whether the concentration of 6-hydroxymelatonin sulfate (6-OHMS) remains stable in urine samples stored over at least 15 yr. To test this, 117 twenty-four-hour urine samples were analyzed, which were obtained from healthy children ages 8 to 9 yr within the periods of 1985-1987,1991-1993, and 1997-1999. 6-OHMS concentrations were determined by enzyme-linked immunosorbent assay. The statistical analyses clearly indicate that the concentration of 6-OHMS remains stable for at least 15 yr if the urine is stored at -20 degrees C.

Objectives: The aim of this study was to check whether leptin is reliably measurable in urine samples of children, adolescents, and adults and to examine whether capillary leptin measurements can be utilized as an alternative tool to assess the leptin status., Methods: Two studies were performed. In both studies, leptin was quantified by an ultrasensitive and highly specific enzyme immunoassay (ELISA; R & D Systems). Anthropometric measures were taken from all study subjects, and body fat was calculated using skinfold thickness measurements. In study 1, leptin was analyzed in 24-hour urine samples of 155 healthy children and adolescents and 26 healthy adults after a methodological modification of the assay necessary for urine analysis. In study 2, venous and capillary blood samples were collected in 26 healthy adults within 10 min on the same day., Results: After adapting the assay system to urine matrix, the detection range was 20-160 pg/ml. Only in 2 of 181 urine samples reproducibly measurable urinary leptin concentrations in the lowest detection range were found. In study 2, a close correlation was found between log capillary and log venous leptin concentrations (r = 0.98, p < 0.001) and between log capillary as well as log venous leptin levels and percent body fat (r = 0.86, p < 0.001)., Conclusions: Our results based on one of the most specific and sensitive ELISAs currently available show that leptin is generally undetectable in the urine from healthy children, adolescents and adults. Thus, urinary leptin excretion cannot be used as a noninvasive marker of the leptin status. Our findings in healthy adults show that the merely moderately invasive determination of capillary leptin allows a reliable assessment of the individual leptin status and may be used instead of venous leptin as a biochemical indicator of body fatness., (Copyright 2002 S. Karger AG, Basel)

It is well established that diet and certain food components have a clear impact on acid-base balance. For adults, the following factors are involved: 1) the chemical composition of foods (i.e., their content of protein, chloride, phosphorus, sodium, potassium, calcium, and magnesium), 2) the different intestinal absorption rates of the relevant nutrients, 3) the metabolic generation of sulfate from sulfur-containing amino acids, 4) the grade of dissociation of phosphorus at the physiologic pH of 7.4, and 5) the ionic valence of calcium and magnesium. All these factors allow us to estimate the potential renal acid load (PRAL) of any given food or diet. The PRAL (calculated for a 24-hour period), together with a relatively constant daily amount of urinary excreted organic acids (in healthy subjects proportional to body surface area or body weight), yields the daily net acid excretion. This article provides an overview of the current concepts of diet influences on acid-base balance and also focuses on the underlying physiologic and biochemical basis as well as on relevant clinical implications.