Longitudinal study of leptin concentrations during puberty: sex differences and relationship to changes in body composition

Leptin may have a role in the initiation of puberty and the regulation of subsequent weight gain, but this hypothesis has not been tested by longitudinal study. We report data from 40 normal children (20 boys and 20 girls) followed from 8-16 yr of age with hormone measurements and auxology every 6 months. Before the onset of puberty, leptin levels were similar in boys and girls: G1, mean (95% confidence interval), 2.63 (2.17-3.20) ng/mL; B1, 2.47 (2.08-2.94) ng/mL (P = 0.64) and increased with age in both sexes (B, 0.107 +/- 0.042; P = 0.02). With the onset of puberty, leptin levels increased in girls (B2-B5, P < 0.0005), but decreased in boys (G2-G5, P < 0.0005). Similar positive independent relationships were seen between leptin and fat mass in girls (B, 0.106 +/- 0.022; P < 0.0005) and boys (B, 0.121 +/- 0.020; P < 0.0005), and negative relationships were found with fat-free mass [girls: B, -1.104 +/- 0.381 (P < 0.005); boys: B, -1.288 +/- 0.217 (P < 0.0005)]. Girls gained more fat mass than boys, whereas boys gained more fat-free mass, and this explained the sex difference in leptin levels. Leptin levels correlated significantly with a large number of other hormones, but none was independent of changes in body composition. In girls, but not in boys, low leptin levels during prepuberty (B1) predicted subsequent gains in the percent body fat during puberty (r = -0.75; P = 0.005). The sexual dimorphism in leptin levels during puberty reflects differential changes in body composition. Prepubertal leptin levels in girls also predict gains in the percent body fat.     

Lack of physiological suppression of circulating IGFBP-1 in puberty in patients with insulin-dependent diabetes mellitus

OBJECTIVE: To evaluate the interaction between serum free insulin, insulin-like binding protein (IGFBP)-1 and leptin concentrations during puberty in insulin-dependent diabetes mellitus (IDDM). DESIGN: Adolescent patients with IDDM (n=101, age >9 years, duration >2 years) from the Outpatient Clinic of the Department of Pediatrics at Oulu University Hospital, and non-diabetic controls, were recruited to the study. Free insulin, IGFBP-1, leptin and insulin antibody concentrations were measured from a fasting serum sample. RESULTS: Free insulin concentrations were lower in the patients than in the controls (4.3+/-2.3 mU/l compared with 6.5+/-3.1 mU/l, P<0.001), and there was an inverse correlation between free insulin and fasting blood glucose in the boys with diabetes (r=-0.53, P<0.001), whereas a positive correlation was observed between free insulin and leptin concentrations in the girls with diabetes (r=0.30, P=0.020). The IGFBP-1 concentrations were greater in the patients than in the controls (16.5+/-10.6 microg/l compared with 4.0+/-3.3, P<0.001), and they correlated significantly with blood glucose (r=0.63, P<0.001) and free insulin (r=-0.35, P<0.001). No significant difference was observed in the leptin concentrations between the patients and controls overall, despite greater total body fat in the girls with diabetes compared with the control girls. CONCLUSIONS: Adolescents with IDDM are characterised by morning hypoinsulinaemia and high circulating IGFBP-1 concentrations, which may contribute to insulin resistance and impaired metabolic control during puberty. The mechanism behind the increased total body fat in the postpubertal female patients remains to be determined.     

High serum leptin levels in children with type 1 diabetes mellitus: contribution of age, BMI, pubertal development and metabolic status

OBJECTIVE: Children with diabetes mellitus are prone to develop obesity and to experience a delay in onset of the pubertal process. In order to understand the role of leptin in these abnormalities, serum leptin levels were analysed in children with type 1 diabetes mellitus. SUBJECTS: Twenty diabetic girls, 23 diabetic boys and 66 healthy children (selected from a reference population of 706 normal children), age-, sex- and BMI-matched with diabetic patients, were studied. MEASURMENTS: Standing height, weight and BMI were determined in each child. Serum testosterone, oestradiol and leptin were measured by specific radioimmunoassays, and HBA1c by high performance liquid chromatography. RESULTS: Both diabetic girls and boys showed higher leptin levels than the normative healthy population and a group of age-, sex- and BMI-matched normal children. In an age-related analysis, leptin levels in diabetic girls rose from 7.4 +/- 1.2 and 8.1 +/- 2.1 microg/l for the 5-7.99 and 8-10.99 year groups, to 12.6 +/- 2.4 microg/l for the 11-13.99 year group, and to 15.6 +/- 4.0 microg/l in the 14-15.99 year group in parallel with body weight. Leptin concentrations were parallel but higher (P < 0.05) than those of healthy girls. Diabetic boys had lower leptin levels than girls and, in contrast with normal boys, did not show a drop after the 10-year period. Leptin levels were 4.9 +/- 2.2, 3.9 +/- 0.2, 5.5 +/- 0.6 and 5.1 +/- 0.9 microg/l for the 5-7.99, 8-10. 99, 11-13.99 and 14-15.99 year groups, respectively. When divided by pubertal stage, leptin levels in the prepuberty stage of diabetic girls (8.6 +/- 1.0 microg/l) were higher (P < 0.05) than those in the controls (4.1 +/- 0.4 microg/l). In overt puberty girls, leptin was higher (P < 0.05) for diabetic (15.9 +/- 2.9 microg/l) than for healthy girls (9.2 +/- 1.1 microg/l). In prepubertal boys, differences were observed in leptin levels (4.9 +/- 0.5 microg/l for diabetic boys and 3.4 +/- 0.6 microg/l for healthy boys). In the overt puberty stage, diabetic boys showed higher (P < 0.05) levels of leptin (5.2 +/- 0.7 microg/l) than the healthy matched controls (2.1 +/- 0.2 microg/l). A multiple step regression analysis in the diabetic children revealed no associations between leptin and other relevant variables such as glycosylated haemoglobin, daily insulin dose, or years of suffering from the disease. CONCLUSION: Serum leptin levels were higher in diabetic than in healthy children. These differences were not attributable to age, adiposity or stage of pubertal development, and were probably conditioned by the metabolic perturbation intrinsic to the diabetic state, or the chronic hyperinsulinemia.     

Hormonal and body composition predictors of soluble leptin receptor, leptin, and free leptin index in adolescent girls with anorexia nervosa and controls and relation to insulin sensitivity

Anorexia nervosa (AN) is associated with very low levels of leptin, a cytokine secreted by adipose tissue and known to suppress appetite. Leptin may play a permissive role in onset of puberty and in resumption of gonadal function in conditions of undernutrition. The soluble leptin receptor (sOB-R) is the main leptin binding protein, and the ratio of serum leptin to sOB-R provides a measure of the free leptin index (FLI), which may be a more accurate determinant of leptin function. Determinants of sOB-R and FLI have not been examined in an adolescent population. We examined levels of sOB-R, leptin, and FLI, and body composition and hormonal determinants of these variables in 23 adolescent girls with AN and 21 healthy adolescent girls of comparable maturity prospectively over 1 yr. Measures of insulin resistance and adiponectin were also examined. We determined changes in levels of sOB-R, leptin, and FLI with weight recovery (defined as an increase in body mass index of >/=10%, n = 11), and with resumption of menstrual cycles (n = 13).Girls with AN had significantly higher levels of sOB-R (P = 0.0008) and significantly lower levels of leptin and FLI (P < 0.0001 for both) than healthy controls, and levels of FLI were reduced more than levels of leptin in girls with AN compared with controls. An inverse correlation was noted between levels of leptin and sOB-R for the group as a whole (r = -0.64, P < 0.0001) but not in girls with AN considered alone. The most important predictor of levels of sOB-R was cortisol in the group as a whole (r = 0.61, P < 0.0001) and in girls with AN considered alone (r = 0.66, P = 0.0008). Other independent predictors of sOB-R levels for the entire group were percent body fat (r = -0.44, P = 0.003) and levels of IGF-I (r = -0.37, P = 0.01). The most important predictors of leptin and FLI were body mass index and percent body fat. An inverse relationship was noted between measures of insulin resistance and sOB-R levels, whereas a positive association was noted between these measures and leptin and FLI. Adiponectin values did not differ in girls with AN compared with healthy controls and did not correlate with sOB-R, leptin, or FLI. Weight recovery resulted in significant decreases in levels of the sOB-R (24.7 +/- 1.7 to 17.6 +/- 1.2 U/ml, P = 0.004), and increases in levels of leptin (4.4 +/- 1.0 to 13.7 +/- 2.9 microg/liter, P = 0.02). Resumption of menstrual function, but not weight recovery alone, was associated with significant increases in FLI (0.19 +/- 0.04 to 0.50 +/- 0.09 microg/U x 10(-3), P = 0.02).We demonstrate an increase in levels of sOB-R and a decrease in the FLI in adolescent girls with AN, and also demonstrate that cortisol is the most important predictor of levels of sOB-R in this condition. Levels of leptin and FLI, conversely, are primarily predicted by body composition. Weight recovery is associated with a decrease in sOB-R and an increase in leptin. Resumption of menses is associated with significant increases in the FLI, suggesting that free leptin may be an important determinant of menstrual recovery.     

Leptin and body fat in type 2 diabetes and monodrug therapy

To better understand the relations among leptin, insulin, and body fat during the metabolic progression to diabetes and during drug monotherapy, metabolic parameters were examined in subjects classified as 1) type 2 diabetes; 2) impaired fasting glucose or mild diabetes mellitus; 3) nondiabetic, matched for body mass index (BMI); and 4) nonobese, nondiabetic. Diabetic subjects were also studied during no pharmacological treatment, after 3 months of randomization to metformin or glyburide, and after 3 months of cross-over to the opposite drug. Log leptin correlated more with percent body fat (slope, 0.042; confidence interval, 0.036-0.047; r(2) = 0.826; P < 0.0001) than with total fat mass, percent truncal or nontruncal fat, or BMI. When normalized to percent fat, leptin did not differ by gender. Leptin normalized to percent fat was 35% less in untreated diabetes than that in BMI-matched controls (P < 0.001). Leptin normalized to percent fat was increased by 25% (P < 0.01) as a result of glyburide therapy compared with pretreatment values, but was unchanged by therapy with metformin. Across a spectrum of subjects with diabetes, impaired fasting glucose/mild diabetes, or BMI-matched nondiabetic controls, normalized leptin significantly correlated with glucose-induced insulin release, but not with insulin sensitivity. Our data suggest that plasma leptin is reduced in untreated type 2 diabetes probably as a consequence of reduced insulin secretion and that circulating leptin concentrations are differentially affected by monodrug therapy.     

Body fat and overweight among children and adolescents with diabetes mellitus.

Body composition was assessed in 68 children and adolescents with diabetes mellitus. Body fat was measured by skinfold thickness and the results were compared with those obtained by bioelectrical impedance methods (r = 0.76, p less than 0.001). Percentage body fat from skinfold thickness estimations was 12-38%. Girls appeared to be most at risk of obesity during puberty with mean body fat 31%, significantly greater than in prepubertal girls (22%, p = 0.001) and pubertal boys (21%, p less than 0.001). Body fat increased progressively through puberty in girls, with those in late puberty (stages 4 and 5) having significantly more percentage body fat than those in earlier puberty (stages 2 and 3, p less than 0.001). Those in late puberty also received significantly more insulin per kilogram body weight (p = 0.05) and had higher HbA1 levels (p less than 0.05) than prepubertal girls.     

Insulin resistance, intra-abdominal fat, cardiovascular risk factors, and androgens in healthy young women with type 1 diabetes mellitus

The increased cardiovascular risk in type 1 diabetes may be related, at least in part, to insulin resistance. The aim of this study was to assess the relationships between insulin sensitivity, abdominal fat, androgens, lipids, and blood pressure in 10 premenopausal women with type 1 diabetes (mean +/- SD, hemoglobin A1c 8.1 +/- 1.0%) and 10 nondiabetic body mass index-matched controls. Insulin sensitivity (glucose infusion rate during euglycemic-hyperinsulinemic clamp) was significantly less in the type 1 diabetes group than in controls (49.3 +/- 14.8 vs. 73.2 +/- 21.6 micromol/min x kg fat free mass, respectively, P = 0.01). The two groups were similar with respect to lipids, androgens, energy expenditure, physical activity, blood pressure, and abdominal adiposity (intra-abdominal fat by four-slice computed tomography and central abdominal fat by dual-energy x-ray absorptiometry). There were no relationships between glucose infusion rate, abdominal adiposity, and androgen levels in subjects with type 1 diabetes, in contrast to controls. Our results demonstrate greater insulin resistance in a group of premenopausal women with type 1 diabetes compared with nondiabetic controls, unrelated to abdominal adiposity, lipids, or androgens.     

Leptin before and after insulin therapy in children with new-onset type 1 diabetes.

Serum leptin levels reflect the amount of body fat. However, several reports suggest that insulin may also regulate serum leptin levels. This study was aimed at testing whether leptin levels are low in newly diagnosed patients with type 1 diabetes and increase after institution of insulin therapy. Nineteen children with new-onset type 1 diabetes were studied. Serum leptin levels were measured at presentation before insulin therapy was initiated (day 0), 1 day after insulin therapy (day 1), 3-5 days after insulin therapy (day 3-5), and at 3 months of follow-up (3 months). The control group consisted of 19 healthy children matched for age and body mass index. On day 0 leptin levels were lower in the patients compared with those in controls (3.3 +/- 0.2 vs. 6.2 +/- 0.9 ng/mL; P < 0.005). After insulin therapy, leptin levels increased significantly by day 1 without significant weight change and became comparable to control values by days 3-5. Before insulin therapy, leptin did not correlate with weight, body mass index, or hemoglobin A1c. After insulin therapy, leptin levels on days 3-5 correlated with insulin dose (r = 0.43; P = 0.03). The results of this study demonstrate that children with new-onset type 1 diabetes have low leptin levels before insulin therapy. Leptin levels increase within 24 h of insulin therapy and become comparable to nondiabetic levels by 3-5 days. This rapid increase in leptin after 24 h of insulinization is independent of changes in body weight and is postulated to be due to a stimulatory effect of insulin on leptin production, nutritional replenishment, or both factors together.     

Higher serum leptin level in women than in men with type 1 diabetes

Leptin is the protein product of the obese (ob) gene, a lipostatic hormone that contributes to body weight regulation through suppressing appetite and/or stimulating energy expenditure in humans and/or rodents. In humans, serum leptin concentrations are increased in relation to increased body fat content. Studies have shown a higher leptin level in women compared with men. However, the gender influence on serum leptin concentrations has never been evaluated in patients with type 1 diabetes. In this study, serum leptin levels and percentage body fat mass were measured in men and women with type 1 diabetes. Fasting serum leptin levels were higher in women (16.7 + 11.6 ng/mL) than in men (3.0 +/- 1.5 ng/mL; P < 0.05) and were independent of exogenous insulin intake and of glucose control. Percentage body fat and fat mass were significant determinants of leptin concentration, whereas age and duration of diabetes were not related to leptin concentration. Subgroups of men (n = 12) and women (n = 11) with total body fat between 20 and 30% were compared. Leptin levels were also higher in women compared with men (13.5 +/- 8.3 ng/mL versus 3.2 +/- 1.7 ng/mL; P < 0.05, respectively). In conclusion, our findings indicate that gender is an important determinant of serum leptin concentration in type 1 diabetics, this gender difference is partly explained by body fat distribution and that type 1 diabetic women may be more resistant than type 1 diabetic men to leptin's alleged lipostatic actions.     

Body composition,insulin, and leptin levels in patients with ankylosing spondylitis

The aim of this study was to compare the effect of chronic inflammation on insulin resistance, serum leptin levels, and body composition (BC) in patients with ankylosing spondylitis (AS) and healthy controls. Twenty-eight AS patients and 17 healthy controls were included in this study. Subjects with hypertension, diabetes, hyperlipidemia, and obesity were excluded. Acute phase reactants and serum levels of glucose, insulin, lipids, and leptin were studied. BC was determined anthropometrically and by foot-to-foot body fat analyzer (BIA, bioelectrical impedance analysis). Quantitative insulin-sensitivity check index, homeostasis model assessment for insulin resistance, and McAuley indices were calculated. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Age, sex distribution, smoking status, serum lipids, insulin concentrations, and insulin resistance indices were comparable between AS patients and controls (p > 0.05). However, acute phase reactants were significantly higher and leptin levels were significantly lower in the AS patients than in controls (p < 0.05). Fat percent assessed by both BIA and anthropometrical methods was lower in the male and female AS patients than in controls, and this reduced fat level reached statistical significance for men (p < 0.05). There were significant correlations between percent body fat, body mass index, leptin, age, and BASMI (p < 0.05; r = 0.6, 0.75, 0.35, -0.41, respectively). On the other hand, body fat percent, waist-to-hip ratio, C-reactive protein, and BASMI were significantly correlated with serum leptin levels (p < 0.05; r = 0.75, -0.42, -0.52, -0.47, respectively). Chronic inflammatory condition in AS may be responsible for the reduced body fat content and lower circulating leptin concentrations. Insulin levels and insulin resistance indices seem similar in patients and controls in the absence of classic vascular risk factors.     

Leptin levels in relation to body composition and insulin concentration in patients with endogenous Cushing's syndrome compared to controls matched for body mass index

Cushing's syndrome (CS) is associated with weight gain and visceral obesity. We examined the relationship between regional fat distribution and serum levels of leptin, cortisol and insulin. Twenty-three consecutive patients with recently diagnosed CS (18 with pituitary adenoma, 5 with adrenal tumor), where compared to obese controls, matched for age, sex and Body Mass Index (BMI). Serum insulin, leptin, cortisol, C-peptide and body composition determined by DEXA were measured. Serum leptin levels were significantly increased in patients with CS (36.9+/-3.8 vs 18.9+/-2.4 ng/ml, p<0.001; women: 40.1+/-4.6 vs 21.7+/-2.9 ng/ml, p<0.01; men: 27.9+/-5.7 vs 10.9+/-2.3 ng/ml; p<0.05), the same were fasting insulin levels (178+/-30 vs 81+/-10 pmol/l; p<0.01) and C-peptide (1.51+/-0.12 vs 0.77+/-0.07 nmol/l; p<0.001). In a subgroup of 12 patients, truncal fat mass was significantly elevated when compared to obese controls (19.2 kg vs 14.7 kg, p<0.01, and 42% vs 36% in percentage of truncal body tissue, p<0.05), whereas total fat mass was insignificantly increased. Serum leptin correlated positively to total body fat (%) as in patients with CS (r=0.94, p<0.001) as in controls (r=0.68, p<0.01). The correlation to truncal body fat (%) was also significant in both groups (CS: r=0.84, p<0.001; controls: r=0.63, p<0.01). Multiple regression showed that percent total body fat was the predictor of leptin concentrations among patients with CS (r2=0.88, p<0.001) whereas insulin did not contribute significantly to the variance in leptin concentrations. In controls, both leptin and insulin (r2=0.65, p<0.001) contributed significantly to the variations in leptin levels. Controlled for the differences in total body fat, patients with endogenous CS have significantly increased serum leptin levels, compared to BMI-matched obese controls. This suggests that hyperleptinemia in CS not primarily reflects changes in body composition, but is the result of different hormonal influences on adipose tissue.     

Pubertal and gender-related changes in the sympathoadrenal system in healthy children

A critical amount of body fat is necessary for the initiation of puberty, and leptin, an adipocyte-derived hormone, is necessary for pubertal development. The sympathoadrenal system modulates body fat stores and leptin secretion and interacts with adrenocortical androgen production, suggesting a possible role in sexual maturation. We studied sympathetic nerve and adrenomedullary activity at rest in 80 healthy children (ages, 5-17 yr; 37 boys and 43 girls) in relation to age, pubertal stage, gender, physical activity, body mass index, and serum levels of sex steroids, dehydroepiandrosterone sulfate, cortisol, leptin, and insulin. Plasma concentrations of the adrenomedullary hormone, epinephrine (E), and its metabolite metanephrine (MN), decreased significantly with advancing puberty and were higher in boys than in girls. E and MN correlated significantly and inversely with dehydroepiandrosterone sulfate, estradiol, testosterone, leptin, and insulin. Plasma norepinephrine, which is primarily derived from sympathetic nerve endings, increased significantly with advancing puberty and increasing testosterone levels in boys. Stepwise multiple regression analysis revealed that E was best predicted by pubertal stage and leptin, and MN by estradiol and leptin. Our data suggest that sympathoadrenal hormones may play a role in the complex process of sexual maturation. Further studies are needed to investigate a possible modulatory role of the adrenal medulla in the body weight-related timing of adrenarche and/or gonadarche.     

Relationship between plasminogen activator inhibitor-1 antigen, leptin, and fat mass in obese children and adolescents

Hyperleptinemia may be associated with cardiovascular risk and is linked with parameters of fibrinolytic processes in adults. We studied whether body fatness, leptin, and insulin interact with plasminogen activator inhibitor-1 antigen (PAI-1-Ag) and tissue-type plasminogen activator antigen (tPA-Ag) in obese children and adolescents. Twenty-three boys (mean +/- SD: age, 10.7 +/- 3.3 years; body mass index [BMI], 28.7 +/- 5.4 Kg/m2) and 19 girls (age, 11.9 +/- 2.7 years; BMI, 29.4 +/- 4.8 Kg/m2) were investigated. Body fat mass (FM) in the children was calculated by bioelectrical impedance analysis, and blood samples were obtained for leptin, insulin, C-peptide, PAI-1-Ag, and tPA-Ag. The children were divided into 3 subgroups according to maturation. Maturity was associated with greater adiposity and higher levels of leptin and C-peptide, but insulin and PAI-1-Ag were not different between prepubertal, pubertal, and late/postpubertal children. PAI-1-Ag was associated with leptin and insulin, but not after adjustment for fatness. PAI-1-Ag was independently associated with tPA-Ag (r = .36, P < .02). Multiple regression analysis showed that tPA-Ag failed to reach the level of significance (P = .07), but FM contributed to the variation in PAI-1-Ag (adjusted R2 = .29). The BMI was the main determinant for the variation in leptin (adjusted R2 = .386) and in insulin (adjusted R2 = .60, all P < .001). Neither gender, maturation, chronological age, or leptin contributed significantly to the variation in either PAI-1-Ag or tPA-Ag. Our data suggest that adiposity and other variables contribute to higher levels of PAI-1-Ag. Leptin seems not to be independently linked with fibrinolytic parameters, but an unfavorable metabolic and fibrinolytic risk profile might emanate from the obese pubertal stage.     

Plasma leptin is associated with insulin resistance independent of age, body mass index, fat mass, lipids, and pubertal development in nondiabetic adolescents

OBJECTIVE: The rising epidemic worldwide in overweight and obese children requires urgent attention. Leptin has been found to be associated with body weight control and possibly affects insulin sensitivity. Since insulin resistance is associated with obesity in adults and possibly in adolescents, we set out to investigate the association of plasma leptin level with various anthropometric indices, body fat mass (FM), lipids, and insulin resistance (IR) index in nondiabetic adolescents. DESIGN: A cross-sectional study from three high schools in Taipei City in Taiwan. SUBJECTS: A total of 402 nondiabetic subjects (162 boys and 240 girls; age range, 10-19 y; mean age, 15.8+/-1.9 y, and mean body mass index (BMI), 24.8+/-4.6 kg/m(2)) were recruited. MEASUREMENTS: The fasting plasma leptin, plasma glucose, insulin, lipids, and anthropometric indices including height, weight, waist (WC) and hip circumferences, and waist-to-hip ratio (WHR) were examined. Total body FM and percentage body fat (FM%) were obtained from dual-energy X-ray absorptiometry. The homeostasis model was applied to estimate the degree of IR. RESULTS: The plasma leptin levels were significantly higher in girls (17.45+/-10.13 ng/ml) than boys (8.81+/-6.71 ng/ml, P<0.001). The plasma leptin levels were positively correlated to BMI, WC, WHR, FM, FM%, and triglycerides (TG). The IR index was positively correlated to BMI, WC, WHR, FM, FM%, TG, and leptin. Using the multivariate linear regression models, we found that plasma leptin remains significantly associated with IR index even after adjusting for age, gender, BMI, FM, WC, Tanner stage, and TG. CONCLUSION: Plasma leptin was associated with IR index independent of age, gender, BMI, FM, WC, Tanner stage, and TG. Plasma leptin levels in adolescents could be a predictor for the development of the metabolic syndrome disorders and cardiovascular diseases.     

Relationships between fasting plasma ghrelin levels and metabolic parameters in children and adolescents

Recent findings suggest that ghrelin may have a beneficial effect on vasculature. In the present study, we examined the associations between plasma ghrelin concentration and metabolic parameters in children and adolescents. We measured fasting plasma ghrelin concentrations in 50 Korean children and adolescents (28 boys and 22 girls, mean +/- SD age 12.6 +/- 2.7 years, body mass index 22.7 +/- 5.1 kg/m 2 ), and analyzed the associations between fasting plasma ghrelin level and anthropometric measurements, metabolic parameters, leptin concentration, and fasting insulin level. We found that fasting plasma ghrelin concentration was negatively correlated with height, weight, body mass index, percent body fat, waist circumference, and hip circumference in both boys and girls. Fasting plasma ghrelin levels were significantly negatively correlated with triglycerides and fasting insulin levels and positively correlated with high-density lipoprotein cholesterol in boys, but not in girls. Our results thus demonstrate that higher plasma ghrelin levels have beneficial effects on metabolic parameters in boys and that the relationships between fasting plasma ghrelin levels and metabolic parameters differed according to sex.     

Body composition, fasting leptin, and sex steroid administration determine GH sensitivity in peripubertal short children.

Serum IGF-I levels in GH-treated subjects demonstrate a wide range of responsiveness to GH. However, the factors influencing GH sensitivity are not well known. The aim of this work was 1) to test whether body composition (determined by dual energy x-ray absorptiometry) or factors related to body composition (fasting blood glucose, FFA, C-peptide, leptin, and insulin sensitivity determined by an insulin tolerance test) influence GH sensitivity; and 2) to study the effect of sex steroid priming on GH sensitivity. We measured serum IGF-I at baseline and 24 h after a single administration of GH (2 mg/m(2)) in 60 healthy prepubertal and early pubertal children (height, -2.1 +/- 1.0 SD score). GH sensitivity, as estimated by the increase in serum IGF-I after GH administration (difference between stimulated and baseline serum IGF-I = delta IGF-I), was also determined after a short-term administration of oral ethinyl E2 in girls and im T in boys. The serum IGF-I concentration was 297 +/- 114 microg/liter at baseline and increased to 429 +/- 160 microg/liter, corresponding to a 46 +/- 29% increase over the baseline value (P < 0.0001, stimulated vs. baseline serum IGF-I). delta IGF-I was not different between gender or pubertal stage. There were positive correlations (P < 0.001) between delta IGF-I and adiposity (total body fat, r = 0.62; trunk fat, r = 0.62), fasting leptin (r = 0.64), and C-peptide (r = 0.54), and a negative correlation with fasting FFA (r = -0.33; P < 0.05) even after adjustment for age, gender, and pubertal stage. These factors remained significant independent predictors of the absolute as well as the percent increase in serum IGF-I in multiple regression analyses. Priming with T and ethinyl E2 had a similar stimulating effect on the serum GH peak in response to the insulin tolerance test. In boys, serum baseline IGF-I increased by 60%, and delta IGF-I was similar after vs. before T administration. By contrast, in girls, serum baseline IGF-I was similar, and delta IGF-I was 60% less after vs. before ethinyl E2 administration. This study indicates that 1) GH sensitivity is determined by fat mass, serum fasting leptin, C-peptide, and FFA; and 2) oral ethinyl E2 and im T have divergent effects on the IGF-I response to a single administration of GH.     

Serum leptin levels in diabetic patients on hemodialysis: the relationship to parameters of diabetes metabolic control

Leptin is a protein hormone produced predominantly by adipocytes that affects food intake and energy expenditure. Its serum levels are significantly higher in patients with chronic renal failure compared to healthy subjects. The aim of this study was to compare serum leptin levels in hemodialyzed patients with type II diabetes mellitus (n=26) with body content-matched hemodialyzed patients without diabetes (n=26) and to explore the relationship between parameters of the long term diabetes metabolic control and serum leptin levels. Serum leptin levels in diabetic patients did not significantly differ from those of non-diabetic patients (25.3+/-8.8 vs 25.7+/-8.7 ng/ml). Serum leptin levels in diabetic patients positively correlated with body fat content, body mass index and predialysis serum insulin levels. No significant relationship were observed between serum leptin levels and blood glucose, glycated hemoglobin, glycated protein, serum urea, creatinine, leukocyte count and total hemoglobin respectively. The multiple stepwise regression analysis revealed that body fat content together with body mass index accounted for 77.8% of variations in predialysis serum leptin levels, while insulin levels and the parameters of diabetes metabolic control had only slight prediction value for leptin concentrations. We conclude that serum leptin levels in hemodialysed patients with type III diabetes mellitus do not significantly differ from those of hemodialysed non-diabetic patients. The body fat content and body mass index are the strongest predictors of serum leptin levels, while parameters of long term diabetes metabolic control play probably only minor direct role in its regulation.     

Developmental changes in the relationship between IGF-I and body composition during puberty.

To examine the hypothesis that anthropometric measures and physical fitness influence circulating insulin-like growth factor-I (IGF-I) during puberty, we measured IGF-I, free IGF-I, IGFBP-1, and IGFBP-3 concentrations in 156 healthy girls (9-16 years old) characterized by aerobic capacity (VO2max), fat-free mass (FFM), percent fat mass and pubertal development. IGF-I, free IGF-I and IGFBP-3 increased with pubertal development while IGFBP-1 declined. Percent fat mass correlated inversely with IGFBP-1 (r = -0.57) and directly with insulin (r = 0.50), while VO2max correlated inversely with percent fat mass (r = -0.63), body mass index (BMI, r = -0.57), and FFM (r = -0.40). When subdivided by Tanner stage, IGF-I correlated directly with weight, height, BMI, and FFM in pre-pubertal girls, but these relationships all diminished or disappeared completely by late puberty. Inverse correlations between IGF-I and percent fat mass, and direct correlations between IGF-I and VO2max as observed previously in adults, were not seen until late puberty. These data suggest that in pre-pubertal and early pubertal girls, IGF-I concentrations in blood reflect overall somatic size. This relationship between IGF-I and body size diminishes with sexual maturation, while correlations between IGF-I and both fitness and fatness emerge.     

Metabolic dysfunction in late-puberty adolescent girls with type 1 diabetes: Relationship to physical activity and dietary intakes

AimsAt puberty, type 1 diabetes (T1D) among young girls can lead to excess body weight, insulin resistance, deterioration of glycaemic control and dyslipidaemia. Although biological factors contribute largely to such metabolic dysfunction, little is known of the role of behavioural factors such as physical activity and diet.MethodsThis study investigated the association between metabolic dysfunction measured after a 12-h overnight fast and behavioural factors, including diet (4-day diary) and physical activity (validated questionnaire), in 19 postmenarchal adolescent girls with T1D compared with 19 healthy girls.ResultsT1D girls displayed higher levels of fat mass, insulin resistance (higher plasma glucose, serum leptin and waist-to-hip ratios) and dyslipidaemia (higher LDL-C and apolipoprotein B levels, lower HDL-C and apolipoprotein A-1 levels). Also, contrary to what is usually observed in T1D adults, serum adiponectin, an important vessel protector, was not raised in T1D adolescent girls compared with healthy controls. Quantity and quality of dietary macronutrient intakes as well as physical activity levels were comparable in both groups, although the T1D girls with the poorest metabolic profiles reported having the healthiest diets (fewer total calories, more protein and less carbohydrates). However, in T1D girls, less physical activity and more time spent watching television were associated with poorer metabolic profiles (higher waist-to-hip ratios, fat mass and leptin levels, and lower adiponectin, HDL-C and apolipoprotein A-1 levels).ConclusionCollectively, these data suggest that physical inactivity is linked to metabolic dysfunction to a greater extent than unhealthy dietary habits in postmenarchal T1D adolescent girls.     

Changes in serum leptin concentration during behavioral therapy in obese children

To determine the pathophysiological implications of serum leptin level in obesity, we monitored the changes in serum leptin level during outpatient treatment with life style modification in children. Fifty-five obese Japanese children (34 boys and 21 girls; mean age, 9.64 years) were studied. The control children consisted of 42 nonobese subjects (27 boys and 15 girls). The serum leptin concentration was 4.35 +/- 0.46 ng/ml (mean +/- SEM) in the control girls and 2.93 +/- 0.21 ng/ml in the control boys. The serum leptin concentrations in the obese boys and girls were higher than those in their lean counterparts. The concentration in the obese boys (16.28 +/- 1.41 ng/ml) was similar to that in the obese girls (20.33 +/- 2.0 ng/ml). The logarithmic value of serum leptin concentration at the first blood sampling in obese children was correlated with percent overweight and percent body fat. In 36 obese children (24 boys and 12 girls) whose serum leptin concentrations were monitored serially during treatment of obesity, the percent overweight was significantly decreased after the initial sampling. In each individual, the changes in leptin concentration were roughly parallel to those in percent overweight. The ratio of the leptin concentration at the second blood sampling divided by the one at the first sampling in each individual was closely correlated with the respective delta percent overweight. These results suggest that the preceding course of obesity determines the serum leptin level of obese children on longitudinal basis, and that the leptin level reflects the degree of obesity on cross-sectional basis.