Clinical measures of adiposity and percentage fat loss: which measure most accurately reflects fat loss and what should we aim for?

OBJECTIVE: To determine which clinical measure of childhood obesity should be monitored to best reflect change in adiposity in a weight management programme and estimate the degree of change needed to be relatively certain of fat reduction. SUBJECTS: 92 obese children with a mean (range) age of 12.8 (6.9-18.9) years and a mean body mass index standard deviation score (BMI SDS) of +3.38 (+2.27 to +4.47) attending a hospital-based clinic on a regular, 3 monthly basis. Measurements: Pairs of weight and height measured up to 2.41 years apart used to derive BMI as kg/m2, and adjusted for age and gender to give weight and BMI SDS (BMI-z score) using British 1990 Growth Reference Data. Contemporaneous adiposity estimated by fatness measured by a bioimpedance segmental body composition analyser. RESULTS: Changes in BMI-z scores, compared to BMI, weight and weight SDS, most accurately reflected loss of fat. Reductions of 0.25, 0.5, 0.75, and 1 BMI SDS equate to expected mean falls in total body fat percentage of 2.9%, 5.8%, 8.7% and 11.6%. Approximate 95% prediction intervals indicated that a fall in BMI SDS of at least 0.6 over 6-12 months (or 0.5 over 0-6 months) is consistent with actual fat loss. CONCLUSION: Change in BMI-z score best reflects percentage fat loss compared to BMI, weight and weight SDS. The wide variation in likely percentage fat loss for a given BMI SDS reduction means a loss of 0.5-0.6 is required to be relatively certain of definite percentage fat reduction.     

Change in obesity‐related metabolic abnormalities associated with body mass index improvement through life‐style intervention: A meta‐regression

The reduction in body mass index standard deviation score (BMI‐SDS) associated with improvement in biomarkers relating to metabolic health in obese children is unknown. We aimed to establish the change in BMI‐SDS associated with improved inflammation, liver function, and insulin resistance to inform clinical guidelines for pediatric weight management interventions and to assess the efficacy of future trials. A large‐scale systematic review was conducted to identify relevant studies. Studies of children with a diagnosis of obesity according to defined BMI thresholds, participating in lifestyle interventions to reduce obesity, were included. Studies must have reported baseline (pre‐) and postintervention (or change of) BMI‐SDS and either fasting glucose, homeostatic model of insulin resistance (HOMA‐IR), alanine aminotransferase (ALT), C‐reactive protein (CRP), or interleukin‐6 (IL‐6). A series of meta‐regressions were conducted to establish links between BMI‐SDS change scores and change in metabolic markers of health. Sixty‐eight articles were identified. From the meta‐regression analyses, across all study subsets, greater mean falls in all four parameters, (HOMA‐IR, Glucose, ALT, and CRP) were observed with greater mean loss of BMI‐SDS, but the trends were only statistically significant for HOMA‐IR and CRP (P = .003; P = .021). However, we could not find minimum changes in BMI‐SDS that would ensure a fall in these outcomes. At this time, we are unable to recommend a definitive value of BMI‐SDS reduction needed to improve the markers of metabolic health. Future trials should aim to report additional indices of derived BMI values, which may better reflect changes in actual adiposity.     

Longitudinal changes in insulin sensitivity, insulin secretion, and beta-cell function during puberty

OBJECTIVE: To determine longitudinal changes in insulin sensitivity (SI), insulin secretion, and beta-cell function during puberty in white and black youth. STUDY DESIGN: The tolbutamide-modified frequently sampled intravenous glucose tolerance test and minimal modeling were used to measure SI, the acute insulin response to glucose (AIRg), and beta-cell function (disposition index, DI) in white (n = 46) and black (n = 46) children (mean [+/-SD] age at baseline = 10.2 +/- 1.7 years). Growth curve models (including 272 observations) with SI, AIRg, and DI regressed on Tanner stage were run after adjusting for covariates. RESULTS: After adjusting for covariates, growth curve models revealed that SI decreased and subsequently recovered by the end of puberty in whites and blacks (both p < .05), AIRg decreased linearly across Tanner stages in both races (both p < .001), and DI decreased across puberty in blacks (p = .001) but not in whites (p = .2). CONCLUSIONS: White and black youth exhibited transient insulin resistance and diminished AIRg during puberty. The progressive decline in DI among blacks versus whites may reflect a unique effect of puberty on beta-cell compensation in blacks. Future studies are needed to identify whether this difference contributes to the increased risk of type II diabetes in young blacks.     

The effects of co-therapy with recombinant human insulin-like growth factor I and insulin on serum leptin levels in adolescents with type 1 diabetes mellitus

We previously demonstrated that in patients with type 1 diabetes mellitus (DM), co-therapy with subcutaneous (s.c.) recombinant human insulin-like growth factor I (rhIGF-I) and insulin improves glycemic control and reduces daily insulin requirements without inducing a significant change in body weight. However, it has been postulated that treatment with IGF-I may promote beneficial changes in body composition. Consequently, we assayed serum leptin, a peptide highly correlated with total fat mass, before and during chronic rhIGF-I administration. We studied 14 adolescents with type 1 DM (age range 12-19 yr). All patients were treated for 12 weeks with twice daily (BID) sc rhIGF-I in combination with standard BID split-mix insulin. At baseline, leptin concentrations were positively correlated with body mass index (BMI) (r(2) = 0.52, p = 0.004), as previously described for non-diabetic individuals. Leptin levels in diabetic females were higher than in diabetic males, and more than two times higher than in non-diabetic female controls. Baseline leptin levels did not correlate with patient age, duration of DM or hemoglobin A1c (HbA1c) measurements. The relationship between leptin concentrations and gender was maintained throughout treatment; however, average leptin levels did not change during 12 weeks of IGF-I + insulin co-therapy. These data suggest that despite treatment-induced improvements in HbA1c and serum IGF-I levels, serum leptin concentrations are unchanged by co-therapy with IGF-I + insulin. Moreover, these results suggest that improved metabolic control with IGF-I therapy is not obtained at the expense of increasing adiposity, a complication seen frequently with intensive insulin therapy.     

Changes in leptin, insulin and body composition in obese children during a weight reduction program

BACKGROUND: Girls have higher leptin concentrations than boys at all stages of biological development and this is also seen in the state of obesity. Little is known about whether gender and biological development of obese children influence changes in leptin associated with a short-term weight reduction program. OBJECTIVE: To study whether leptin concentration, body composition and insulin levels in obese children were influenced by a 3-week intervention program including diet and sports. STUDY DESIGN: Sixty-two obese children (32 boys and 30 girls) were examined before and after the intervention program. Body composition was measured by bioelectrical impedance and BMI-SDS was calculated. Serum leptin and serum insulin were determined by RIA. RESULTS: Girls had higher leptin levels than boys, before and after the weight reduction program. Body mass, fat mass (FM), leptin and insulin were decreased after the intervention in both sexes. We found a greater change in serum leptin in girls but the change in FM was of greater magnitude in boys. However, percentage changes in leptin were not significantly different between the sexes. Before the intervention, leptin concentrations were correlated with %FM, FM and moderately with BMI-SDS in all children. Only in pubertal boys did correlation of leptin with %FM increase after the intervention (from r=0.57 to r=0.75, p<0.01). Changes in leptin were found to be associated with initial leptin values in boys (r=0.95, p<0.01) and in girls (r=0.93, p<0.01), independent of Tanner stages. CONCLUSION: Serum leptin levels were positively correlated with adiposity in obese children and a diet and sports intervention program decreased serum leptin, insulin and body fat in all children. Changes in leptin were best described by the initial leptin concentration. The increase in correlation of leptin with %FM in obese pubertal boys after the intervention could have its underlying mechanism in an increased sensitivity to leptin and anabolic hormones.     

Childhood hypo‐adiponectinaemia but not hyper‐leptinaemia is associated with insulin insensitivity 6 years later

Kynde I, Heitmann BL, Bygbjerg IC, Andersen LB, Helge JW. Childhood hypo‐adiponectinaemia but not hyper‐leptinaemia is associated with insulin insensitivity 6 years later. Background: Biomarkers of metabolism and inflammation may predict children with increased diabetes risk. Objective: To study plasma adiponectin, leptin, IL‐8, and hepatocyte growth factor (HGF) in childhood and their independent associations with insulin insensitivity, cross‐sectional and in 6‐yr prospective. Subjects: Danish 8‐ to 10‐yr‐olds and 14‐ to 16‐yr‐olds from the European Youth Heart Studies I and II. Methods: Cross‐sectional (n = 386) and prospective (n = 246) linear regressions of baseline concentrations of plasma biomarkers and insulin insensitivity at baseline and 6 yr later. Adjustments were made at four progressive steps for sex, sexual maturity, body mass index (BMI), other biomarkers, physical activity, and school location as well as baseline insulin insensitivity in prospective analyses. Insulin insensitivity was measured using homeostasis model assessment standardized to the sample mean [homoestasis model assessment (HOMA) Z‐scores]. Plasma biomarkers were quantified using solid‐phase protein immunoassays. Overweight was defined as the highest BMI tertile. Results: Among overweight but not lean children at baseline, one SD difference in baseline plasma adiponectin was associated with ?0.41 SD difference in HOMA Z‐scores 6 yr later (p = 0.006). At baseline, one SD difference in plasma leptin was associated with 0.36 SD difference in HOMA Z‐scores (p =< 0.0001) among 8‐ to 10‐yr‐olds, but a prospective association was not found. Conclusions: We found a direct relationship between childhood hypo‐adiponectinaemia and insulin insensitivity in adolescence. This association was stronger for overweight than for normal weight children. Hyper‐leptinaemia was associated with concurrent insulin insensitivity at baseline but not 6 yr later.     

Pubertal adolescent male-female differences in insulin sensitivity and glucose effectiveness determined by the one compartment minimal model

Most studies of insulin sensitivity in puberty have been cross-sectional and have not been able to longitudinally address changes that might occur. In addition, these studies were unable to separate out glucose's ability to stimulate its own disposal (glucose effectiveness, S(G)) from insulin sensitivity (S(I)) or to separate the hepatic and peripheral effects of insulin. To address these problems, we used the frequently sampled i.v. glucose tolerance test with [6,6]D2 glucose to study S(G)* and S(I)* in 24 children (Tanner stage 1-3) at 6-mo intervals over an 18-mo period. Mean overnight GH and fasting GH binding protein (GHBP), IGF-1, and leptin levels were also measured. S(G)* did not differ between the sexes or Tanner stages. S(I)* did not differ between Tanner stages for either sex and was higher in boys than in girls. Hepatic insulin resistance did not differ between sexes or Tanner stages. S(G)* was not related to any of the other variables measured. S(I)* was negatively related to BMI, GHBP, IGF1, and leptin. These results demonstrate that insulin sensitivity is greater in prepubertal and early pubertal boys than in girls and is primarily determined by body mass effects.     

Serum leptin levels during childhood and adolescence: relationship with age, sex, adiposity and puberty

We studied serum leptin levels in 189 healthy children to evaluate related factors during childhood and adolescence. Leptin correlated with body mass index (BMI), triceps skinfold thickness (p<0.001) and body weight (p<0.01). Obese children and girls had higher leptin levels than non-obese children and boys, respectively (p<0.001). In girls, leptin correlated positively with age, skinfold thickness and BMI (p<0.001). In boys, leptin correlated negatively with age (p<0.001) and positively with skinfold thickness (p<0.05). Prepubertal boys had higher leptin levels than prepubertal girls and pubertal boys (p<0.05). Pubertal girls had higher leptin levels than prepubertal girls and pubertal boys (p<0.001). Leptin levels in girls were higher at Tanner stages 4 and 5 than at stage 1 (p<0.001). In conclusion, serum leptin levels are related with adiposity, have obviously age-related gender differences during childhood and adolescence, and may be involved in the maturation of reproductive capacity.     

Former small for gestational age (SGA) status is associated to changes of insulin resistance in obese children during weight loss

Reinehr T, Kleber M, Toschke AM. Former small for gestational age (SGA) status is associated to changes of insulin resistance in obese children during weight loss. Objective: Former small for gestational age (SGA) children are at risk of both obesity and insulin resistance. Longitudinal studies are required to assess a possible relationship between former SGA status and insulin resistance independent of weight status. We hypothesized that obese children with former appropriate for gestational age (AGA) status improve their insulin resistance during weight loss more effectively compared to obese children with former SGA status. Methods: A 1‐yr longitudinal follow‐up study design was adopted in the primary care setting and 341 obese children [8% SGA, mean age 10.5 ± 0.1 yr, body mass index (BMI) 27.7 ± 0.2, BMI‐standard deviation score (SDS) 2.47 ± 0.02] were taken for the study. Outpatient 1‐yr intervention was based on exercise, behavior and nutrition therapy. We measured insulin resistance index following the Homeostasis model assessment model (HOMA), blood pressure, lipids, glucose, and insulin in all children before and after the 1‐yr intervention. Results: In a multiple linear regression analysis adjusted for age, gender, and pubertal stage, changes of HOMA were significantly related to changes of BMI‐SDS (?2.55 per loss of 1 BMI‐SDS unit; p < 0.001) and SGA status (+2.05 for SGA children; p < 0.001). Changes of BMI‐SDS together with gender and age explained 10% of the variance of changes of HOMA, while SGA status explained an additional 4%. After adjustment for age, sex, pubertal stage, and BMI‐SDS, former SGA status was not significantly related to any other considered cardiovascular risk factor. Conclusions: Change of weight status predicted change of HOMA in obese children participating in a lifestyle intervention. Changes of HOMA were also predicted by former SGA status supporting that former SGA status influences insulin resistance.     

Body composition, dehydroepiandrosterone sulfate and leptin concentrations in girls approaching menarche

There is strong evidence that the initiation of adrenarche and gonadarche during puberty in girls depends on body mass in general and body fat in particular. The aim of this study was to analyze changes in body composition, i.e. body fat (BF), fat percentage (BF%), and lean tissue mass (LM) in girls during pre-menarcheal stages of development, including the earliest stage lacking clinical manifestations of changes in primary, secondary, and tertiary sexual characteristics. Puberty was assessed according to clinical and ultrasonographic staging of sex features developed by us. Concentrations of leptin and DHEA-S were compared and related to changes in body composition. SUBJECTS AND METHODS: The study was carried out on 65 healthy girls aged 8 years and older who were followed every 3 months over a 5-year period. Age, height, weight, and BMI were recorded. Body composition (BF, BF%, LM) was determined with an infrared method. Tertiary sexual features were staged according to Tanner. Vaginal secretion was assessed according to Peter et al. Transabdominal ultrasound of the uterus and ovaries was performed with the bladder unvoided. Groups were formed according to developmental stage: E0A = pre-estrogenization (no ultrasonographic or clinical evidence of estrogenization); E0B pre-estrogenization with 'luminosity' of mucus in cervical canal; E1 = onset of estrogenization; E = full estrogenization; M = menarche +/- 3 months. Concentrations of DHEA-S and leptin were determined by radioimmunoassay. RESULTS: BF in prepubertal girls averaged 16%. At menarche, BF was 23.9%. Body weight at menarche was 50.6 kg and the LM/BF ratio was 3.0. High leptin concentrations were found in E0B and M groups. Leptin concentrations were lowest during full estrogenization (E). Positive correlations of leptin with BF and LM were found in girls during developmental stages preceding menarche. Mean concentration of DHEA-S started at 1,091.6 microg/l during E0A stage, dropped significantly on passing to E0B (p <0.05), and increased by menarche. DHEA-S levels were found to correlate with BF, LM, and leptin in E0A, E0B, and E1 groups. Correlation coefficients were highest (DHEA-S/BF r = 0.61; DHEA-S/LM r = 0.54; DHEA-S/LEP r = 0.57) in the E0A group, i.e. about 5 months before the appearance of 'luminosity' of cervical mucus, considered to be the first ultrasonographic sign of puberty. Apparently, leptin stimulates somatic maturation during this stage of gonadarche which terminates with menarche. The action of DHEA-S is exerted during the early stages of female puberty.     

Changes in hepatic risk factors, metabolic variables, body composition, and physical fitness in obese children after a one-year weight loss program

Obesity can cause insulin resistance and cardiovascular and liver disease. The aim of this study was to analyze changes in laboratory values, body composition, and physical fitness before and after a one-year weight loss program with nutritional education, psychological care, and physical exercise. Twenty-two obese children (16 boys, 6 girls; median age 11.9 [range 7-15] years; BMI SDS +2.4 [1.6-3.1]) participated in the program. Outcome measures included liver enzymes, insulin resistance (HOMA), lipids, body composition, physical strength and endurance. All children had an inverse HOMA/body composition correlation; Group 1 (reduced BMI SDS after one year) had lower triglycerides, liver enzymes and improved body composition and fitness (p < 0.05). Group 2 (unchanged or increased BMI SDS) had worse body composition and increased endurance and strength of trunk extension (p < 0.05). Weight loss reduced risk factors for liver disease and improved insulin sensitivity. Body composition proved useful as a non-invasive indicator for insulin sensitivity.     

Serum leptin concentrations in children with Prader-Willi syndrome and non-syndromal obesity

There is limited information on the underlying physiological mechanisms promoting obesity in patients with Prader-Willi syndrome (PWS). The aim of this study was to investigate whether body fat regulation in children with PWS is similar to that in children with non-syndromal obesity and non-obese children. We studied three groups: 1) 72 non-obese children and adolescents; 2) 68 children with non-syndromal obesity; and 3) 11 patients with PWS. Height and weight were measured and body mass index (BMI) and BMI SDS were calculated. Fasting serum leptin concentrations were determined. Median leptin serum concentrations were similar in PWS patients and children with non-syndromal obesity. Median leptin serum concentrations were higher in these two groups than in the non-obese group. Log leptin serum concentrations and BMI SDS showed significant correlations in the three groups of patients; correlation coefficients were 0.525, 0.285 and 0.854, respectively. In conclusion, median leptin serum concentrations are similar in PWS patients and children with non-syndromal obesity. The relationship between log serum leptin concentrations and BMI SDS was different in the three groups of patients studied.     

Leptin levels decline steadily during prolonged fasting in lean children

OBJECTIVE: To evaluate the effects of fasting on serum leptin levels in lean children. STUDY DESIGN: Seventeen children, age 7.7 +/- 4.3 years with mean body mass index (BMI) of 16.7 +/- 2.7 kg/m(2), underwent standard diagnostic fasts for suspected hypoglycemia. Blood was sampled at 6-hour intervals for glucose, insulin, C-peptide, leptin, free and total insulin-like growth factor-1, insulin-like growth factor-binding protein-1, growth hormone, cortisol, ketones, and free fatty acids. RESULTS: Subjects fasted 15 to 40 hours, and initial leptin levels were related to BMI and age. Leptin declined by 0.5 ng/mL per each fasting hour (P = .008), using a longitudinal mixed effects model. Leptin dropped significantly from an initial mean +/- SEM during the first 6 hours of 15.9 +/- 5.5 ng/mL to 3.5 +/- 0.9 ng/mL at the end of fasting. Mixed longitudinal effects models demonstrated that leptin was significantly related to insulin over time (P < .0001) as well as C-peptide (P < .0001). Significant relations were also seen with total insulin-like growth factor-1 over time, beta-hydroxybutyrate and insulin, and insulin-like growth factor-binding protein-1 and insulin. CONCLUSIONS: After 6 hours, leptin levels steadily decline during prolonged fasting in lean children. The decline probably is related to the suppression of insulin secretion. Although baseline leptin levels were related to BMI and age, in the final fasting sample, leptin levels showed minimal variation in this pediatric cohort encompassing a wide age range.     

Insulin and insulin resistance index are not independent determinants for the variation in leptin in obese children and adolescents

Recent findings have questioned the independent influence of insulin on leptin. We studied whether insulin contributes to leptin in obese children, independent of confounding parameters, such as total adiposity, fasting insulin resistance index, and fat free mass. In 100 obese boys and 103 obese girls, blood levels of leptin, insulin, glucose, and triglycerides were determined. The fasting insulin resistance index (FIRI) was calculated, and body composition was assessed by means of impedance. Leptin and glucose were higher in girls, and all estimates of adiposity were significantly associated with leptin. However, when adjusted for adiposity, the relationship between insulin and leptin, and also between FIRI and leptin, remained significant in boys and girls (p<0.05). Although several regression models were tested, neither insulin nor FIRI were found to contribute significantly and independently to leptin. BMI together with triglycerides and FFM were the main determinants for the variation in leptin in boys (adj. R2=0.46, p<0.0001). In girls, BMI explained a great magnitude of the variation in leptin (adj. R2=0.60, p<0.0001). These findings indicate that in the state of childhood and adolescent obesity, total adiposity but not insulin or insulin resistance index is the main determinant for leptin. In contrast to obese girls, the fat free mass and triglycerides contribute significantly to the variation in leptin in obese boys. The biological significance for these findings should be elucidated in longitudinal studies.     

Weight requirements for return of menstruations in teenage girls with eating disorders, weight loss and secondary amenorrhoea

AIM: To investigate the weight requirements for return of menstruation in teenage girls with eating disorders (ED), weight loss and secondary amenorrhoea. METHODS: Growth charts from the school health services and measurements of weight and stature at assessment and during follow-up were obtained for 127 girls with ED, secondary amenorrhoea and subsequent return of menstruation. Measurements were used to estimate weight and body mass index (BMI) before puberty, at menarche, at the highest weight prior to the onset of the ED, at the last menstruation preceding amenorrhoea, at the lowest weight during treatment, and at return of menstruation. RESULTS: Before onset of the ED, the girls were taller, heavier and less lean than the population average as evidenced by standard deviation scores (SDS) for weight, height and BMI above zero. Weight loss started from an average weight of 58.9 +/- 9.8 kg (mean +/- SD), a last menstruation occurred at 51.5 +/- 6.9 kg, the lowest weight during treatment was 45.6 +/- 7.0 kg and menstruation returned at 52.9 +/- 6.0 kg. Return of menstruation occurred within a wide weight range. However, if weight at return of menstruation was expressed in SDS, it could be predicted by a linear regression on weight SDS at loss of menstruation (r2 = 0.76; p < 0.001). CONCLUSIONS: The weight level required for return of menstruation is highly individual but can be predicted by the weight at which menstruations cease. In the treatment of ED, there is a need for such individual weight targets--a target based on the population weight for height and/or age may be too generalized and too low.     

Bioelectrical impedance analysis of body fatness in childhood congenital adrenal hyperplasia and its metabolic correlates

There is a tendency to adiposity in patients with congenital adrenal hyperplasia (CAH) despite physiological corticosteroid doses. This study investigated body fatness in children with CAH under corticosteroid replacement therapy. Seventeen children with CAH (female:male, 9:8; age range 1.6–10.5 years) and 18 controls (female:male, 9:9; age range 1.4–10.2 years) were studied. Serum lipids, leptin, insulin, anthropometry, body circumferences, skinfold thickness, and body fat ratio as measured with bioelectrical impedance analysis (BIA) were the study parameters. Weight standard deviation scores (SDS), body mass index (BMI), BMI–SDS, body circumferences, skinfold thickness, and body fat ratio were higher and leptin was positively correlated with all of the body circumference and skinfold thickness parameters as well as body fat ratio in the study group. Waist/hip ratio was lower in the study group. Body fatness is a serious problem starting in early childhood in CAH patients and further refinement of the glucocorticoid replacement regimens as well as lifestyle measures are needed.     

Inappropriate leptin secretion in thalassemia: a potential cofactor of pubertal timing derangement

The objective of the present study was to gain a better understanding of the role played by scarce leptin production in the deranged sexual development observed in patients with thalassemia. We studied 101 patients at different stages of puberty. Patients of both sexes were divided into three groups according to Tanner stages: T1-2 (20 males and 12 females), T3-4 (9 males and 4 females) and T5 (48 males and 8 females). Serum levels of leptin, ferritin, testosterone and estradiol were assessed. Leptin levels were adjusted for body mass index (BMI) using reference ranges stratified on the basis of gender and pubertal development. Deviations from the mean reference values were evaluated by calculating the standard deviation scores. Mean leptin standard deviation scores were significantly lower than expected in pubertal stage T1-2 and T3-4 in males and T3-4 and T5 in females. The peak leptin level was delayed in boys (13 years). In girls, parallelism between leptin and BMI was present until age 7-10 years; thereafter, although BMI constantly increased, leptin levels fell dramatically. Mean ferritin levels were significantly higher in pubertal stage T1-2 among males and in T5 among females. These findings show that in thalassemia adipose tissue is unable to assure adequate leptin production just when the highest leptin secretion is required and suggest that this inappropriate leptin secretion may be a cofactor of the derangement in pubertal timing observed in patients with thalassemia.     

Correlates of adiponectin and the leptin/adiponectin ratio in obese and non-obese children

Adiponectin is an adipocyte secreted protein that has been reported to increase fatty acid oxidation and improve insulin sensitivity. Our aim was to study the relationship between adiponectin and leptin, body fat, insulin and lipoproteins in obese compared to non-obese children matched for age and gender. Adiponectin serum concentrations were significantly lower in the obese compared to the non-obese children (9.1+/-3.7 vs 17.1+/-12.3 microg/ml, p <0.05), in contrast to serum leptin concentrations which were greater in the obese compared to the non-obese subjects (31.8+/-11.1 vs 8.2+/-5.7 ng/ml, p <0.001). When considered as a single group to assess adiponectin concentrations over a spectrum of body size, adiponectin values correlated inversely with body weight (r = -0.33, p <0.05) and BMI (r = -0.35, p <0.05). Adiponectin values correlated directly with HDL-C (r = 0.47, p <0.005), but not with total cholesterol, IGF-I, or leptin binding activity. Since leptin and adiponectin change inversely in relation to BMI, the leptin/adiponectin (L/A) ratio was determined as a potential index relating adiposity to the development of complications of obesity. The L/A ratio was eight-fold greater in the obese compared to the non-obese children, and correlated more strongly with BMI (r = 0.779, p <0.0001) and with HDL-C (r = -0.53, p <0.001), than did adiponectin alone. The L/A ratio also correlated significantly with triceps skinfold thickness (TSF) (r = 0.77, p <0.001) and percent body fat (r = 0.79, p <0.0001) in non-obese children. These data suggest that adiponectin concentrations are already differentially regulated in childhood obesity. The index of increased leptin concentration corrected by reduced adiponectin values (L/A ratio) merits investigation as a marker for morbidities associated with childhood obesity.     

No relationship between leptin and cortisol in obese children and adolescents

Recent findings have shown that leptin downregulates the steroid producing system in the adrenal. We studied the interactions of leptin, insulin and cortisol in obese children and adolescents at different stages of maturation. In 44 boys (age 11+/-3.1 yr, body mass index [BMI] 29+/-5.3 [mean +/- SD]) and 35 girls (age 11.4+/-2.6 yr, BMI 29+/-4.3), blood levels of leptin, insulin, cortisol, and glucose were determined. Fat mass (FM) was calculated by bioelectrical impedance. No significant differences were found between boys and girls with respect to humoral and anthropometric characteristics. When children were divided according to maturation stage (prepubertal, pubertal, and late/postpubertal) insulin was higher in the more mature groups (p<0.01) and leptin was higher in the pubertal group (p=0.03). In the prepubertal and pubertal groups, the expected positive relationship between adiposity and leptin was found although the magnitude of this association decreased with maturity. In none of the groups studied was cortisol significantly correlated to leptin. Insulin (p=0.03) and glucose (p=0.01) were positively associated with cortisol in the prepubertal group after adjustment for adiposity. However, in the pubertal group an inverse correlation was found between insulin and cortisol (p=0.03), and between insulin and glucose after control for adiposity. In the late/ postpubertal group, no significant correlations were found between estimates of adiposity and humoral parameters even after adjustment for gender. Stepwise multiple regression failed to detect a significant influence of cortisol to explain the variation in leptin, and vice versa. BMI contributed to the variation in leptin (adj. R2 =0.275, p<0.0001), and glucose added 5% to the variation in cortisol (p=0.03). The results do not confirm the inverse association between leptin and cortisol found in adults. Although BMI reflects levels of leptin, it is likely that several other factors in conjunction with fatness modulate the relationship with leptin. Whether leptin per se exerts an influence on the hypothalamic-adrenal-adipo axis remains to be investigated in longitudinal studies.     

Leptin in African-American children

Leptin, the protein product of the obesity gene, produced by adipose tissue, regulates body weight and energy expenditure through CNS feedback mechanisms. In obesity, leptin levels are elevated suggestive of leptin resistance. Because of increased prevalence of obesity in African-Americans, the aim of this study was to assess leptin and its relationship to adiposity in African-American children. We measured plasma leptin levels in 42 African-American children (23 M, 19 F), age 11.8 +/- 0.3 yr, and compared them with 30 American-White children matched for age, body composition and puberty. Body composition was assessed by bioelectrical impedance and plasma leptin by RIA. Data are presented as means +/- SEM and statistical significance is implied by p < 0.05. There was no racial difference in plasma leptin levels (Blacks: 9.8 +/- 1.6, Whites 9.8 +/- 1.9 ng/ml). Leptin correlated with %BF in Black (r = 0.75, p = 0.005) and White (r = 0.79, p = 0.005) children. There were no gender or puberty related differences in leptin levels in African-American children. We concluded that leptin levels are comparable between African-American and American White children of similar body composition. The major determinant of serum leptin levels in these children is degree of adiposity with no gender or puberty related differences. Longitudinal studies are needed to assess leptin's role during puberty in both genders.