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 binding activity (LBA) in plasma of nondiabetic and diabetic adolescents and obese children: relation to auxologic and hormonal data

Leptin circulates in serum bound to high molecular weight proteins. Hypothesizing that leptin binding proteins may regulate the functional efficiency of leptin, we characterized auxologic and hormonal factors that influence leptin binding in three disparate groups: normal adolescents, obese children, and teenagers with type I diabetes mellitus (IDDM). Specific leptin binding activity (sLBA) was assessed by column chromatography after incubation of serum with 125I-leptin in the presence and absence of excess unlabeled leptin. Mean sLBA was 17.0 +/- 7% (SD) in the healthy adolescents (n=41), 6.6 +/-4.3% in the obese children (n=26), and 14.9 +/-7.3% in the diabetic teenagers (n=17). At any value of sLBA, obese children had higher serum leptin levels than non-obese adolescents or diabetic teenagers, consistent with "leptin resistance" in the obese group. sLBA was higher in males than in females only in those with diabetes (18.6 +/- 7.3 vs 10.9 +/- 5.1%, p<0.05). sLBA correlated inversely with serum insulin-like growth factor-I values in the normal group (r= -0.45, p<0.01) and with insulin in the obese children (r= -0.53, p<0.01). There was no correlation between sLBA or serum leptin values and HbA1c, in the diabetic group. The serum leptin concentration was the principal determinant explaining the total variability of sLBA in all three cohorts. However, body mass index (BMI = weight/ height2) accounted for more of the total variability of percent specific binding in the healthy adolescents than in the other groups. We conclude that sLBA reflects circulating leptin levels, body composition, and hormonal milieu. Thus, in addition to leptin, qualitative and quantitative characteristics of leptin binding may play a physiological role in the regulation of appetite and in the "leptin resistance" of obesity.     

Pubertal changes in serum leptin levels in adolescents with type 1 diabetes mellitus: a controlled longitudinal study

The mechanism of the pubertal delay seen in some adolescents with type 1 diabetes mellitus is not entirely clear. Since leptin has been implicated as a neuroendocrine modulator of puberty, we measured serum leptin levels longitudinally in 24 post-'honeymoon' patients with diabetes mellitus (M/F = 15/9) with a mean (+/- SD) age of 10.5 +/- 0.9 years and 26 controls (M/F = 15/11) with a mean age of 10.0 +/- 1.1 years. Physical examinations; serum leptin, IGF-I, IGFBP-3 and IGFBP-1 levels; and bone age X-rays were performed annually for up to 48 months. Glycosylated hemoglobin (HbA1c) was measured 2-4 times a year in patients with diabetes mellitus. Serum leptin levels strongly correlated with the body mass index z-scores (BMI-Z) in both controls (r = 0.666, p <0.00001) and diabetic patients (r = 0.577, p <0.00001). Girls had increased serum leptin levels for a given BMI compared to boys (p <0.005). There were no significant differences in serum leptin levels of patients with diabetes mellitus compared to controls, nor were differences seen when the groups were stratified by age, Tanner stage, or gender. There were also no significant correlations between serum leptin levels and degree of metabolic control (i.e. HbA1c) or insulin dose standardized for body weight. Although there was no significant diabetes-related or metabolic control-related delay in bone age z-score or pubertal development, there was a significant negative correlation between HbA1c and growth velocity z-score, indicating that children with poor diabetes control had modest but significant slowing of growth. It is concluded that neither pubertal development nor serum leptin levels are significantly altered in adolescents with diabetes mellitus managed with standard therapy. The potential role of leptin in initiation of pubertal development is not easily demonstrable in observational studies.     

Relation of serum leptin and insulin-like growth factor-1 levels to intima-media thickness and functions of common carotid artery in children and adolescents with type 1 diabetes

BACKGROUND AND AIM: Leptin and insulin-like growth factor-1 (IGF-1) have been suggested to be involved in the pathogenesis of atherosclerosis. The aim of this study was to evaluate the relationship between serum leptin, IGF-1 and intima-media thickness (IMT) and functions of common carotid artery (CCA) in children and adolescent patients with type 1 diabetes. MATERIAL AND METHODS: Serum leptin and IGF-1 levels were measured in 45 diabetic patients (23 girls and 22 boys). Age, diabetes duration as well as major cardiovascular risk factors, including anthropometric and metabolic parameters, were matched between girls and boys. The relation of serum leptin and IGF-1 levels to CCA structure and functions were measured by ultrasonography as IMT, cross-sectional compliance (CSC), cross-sectional distensibility (CSD), diastolic wall stress (DWS) and incremental elastic modulus (IEM). RESULTS: Serum leptin levels of diabetic girls were higher than those in the boys (21.8 +/- 14.5 microg/l vs 8.9 +/- 10.6 micro/l, p = 0.002). However, the difference for serum IGF-I levels was not significant between diabetic girls and boys (240.7 +/- 96.8 ng/ml vs 234.7 +/- 93.2 ng/ml; p > 0.05). In all subjects, leptin levels were correlated with CSC (p = 0.04), CSD (p = 0.04) and IEM (p = 0.01), and IGF-1 levels were only correlated with CSC (p = 0.01). Leptin did not show any correlation with ultrasonographic measurements in both girls and boys separately. IGF-1 was correlated with CSC (p = 0.001), CSD (p = 0.002) and IEM (p < 0.001) in boys but not in girls. In a multivariate regression model, IGF-1 emerged as independent correlates for mean CSD and IEM in boys but not in girls. CONCLUSION: Serum leptin and IGF-1 levels in children and adolescent patients with type 1 diabetes are associated with functions of common carotid artery, and the association of IGF-1 levels is influenced by sex.     

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.     

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.     

Partial remission phase and metabolic control in type 1 diabetes mellitus in children and adolescents

A better understanding of the remission phase, while residual beta-cell function is still present in recently diagnosed type 1 (insulin dependent) diabetes mellitus (IDDM), is very important because of the potential for pharmacological intervention to preserve this function. To evaluate the natural course and characteristics of the remission phase in children and adolescents with IDDM, a retrospective study was performed on patients diagnosed with IDDM under the age of 18 years during the years 1991-1998. Sixty-two patients whose medical records were available were included in the study. Data were collected by reviewing the hospital records of patients from the time of diagnosis through the first 24 months after diagnosis. The duration of symptoms and history of infection prior to presentation, diabetic ketoacidosis (DKA) at diagnosis, length of hospitalization, initial glucose level, basal C-peptide levels at diagnosis, daily insulin requirements per kg body weight and HbA1c at diagnosis and at each visit were recorded. Thirty-five patients (56.5%) entered partial remission. We observed similar remission rates in those aged <10 and > or =10 years at diagnosis and in boys and girls. History of infection and presentation with DKA were associated with a lower rate of remission (p<0.001, p<0.0001, respectively) and were more commonly observed under the age of 10 years (p<0.0001, p<0.0001, respectively). The average insulin requirements per kg body weight calculated at diagnosis decreased with increasing age (r = -0.31, p = 0.012). The length of time until remission was 1.36+/-1.03 (mean +/- SD) months and positively correlated with insulin requirements at discharge from the hospital (r = 0.63, p<0.0001). Mean duration of remission was 11.67+/-5.82 months and was much longer in boys than girls (p<0.05). Six patients, all boys, entered total remission for 3.80+/-3.73 months. HbA1c concentrations in the first year of the disease were significantly lower in patients who underwent a remission phase (7.31+/-1.24% vs. 8.24+/-1.47%, p <0.05). However, this difference was not observed during the second year of the disease. In conclusion, history of infection prior to presentation and DKA at diagnosis were associated with young age and were the most important factors negatively influencing the remission rate in newly diagnosed IDDM patients.     

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目的探讨丙戊酸治疗对癫癎患儿血浆胰岛素和瘦素水平的影响。方法测定2003-04—2004-02在山东大学齐鲁医院儿科癫癎治疗中心就诊且服用丙戊酸的32例癫癎患儿和33例对照组(儿外患儿)血浆胰岛素、瘦素水平并计算胰岛素抵抗值、体重指数,并对服用丙戊酸的癫癎患儿胰岛素抵抗值、瘦素与丙戊酸的剂量、疗程、体重指数进行相关分析。结果丙戊酸治疗组体重指数、胰岛素、胰岛素抵抗值、瘦素水平高于对照组;胰岛素抵抗值、瘦素水平与体重指数、丙戊酸疗程显著正相关,与剂量无相关性;偏相关分析示对照组胰岛素、胰岛素抵抗值与瘦素显著负相关,而丙戊酸治疗组胰岛素、胰岛素抵抗值与瘦素显著正相关。结论丙戊酸治疗可引起肥胖程度增加、胰岛素抵抗及瘦素抵抗;胰岛素抵抗、瘦素抵抗与肥胖程度增加有关,与丙戊酸疗程正相关;胰岛素抵抗与瘦素水平显著正相关。     

Continuous subcutaneous insulin infusion in children and adolescents with diabetes mellitus: decreased HbA1c with low risk of hypoglycemia

AIM: To evaluate blood glucose and HbA1c levels, insulin dosage, hypoglycemia rate and body mass index (BMI) at baseline, and at 3 and 6 months after initiation of continuous subcutaneous insulin infusion (CSII) in children and youth with type 1 diabetes mellitus (DM). METHODS: A 6-month trial of pump therapy was carried out in 40 patients with type 1 DM and one with cystic fibrosis (CF) induced DM (25 males), aged 4-25 years (mean 13.5 +/- 4.2 [SD]; 4-8 years, n = 6; 8-10 years, n = 8; 10-12 years, n = 4; 12-15 years, n = 11; >15 years, n = 12). RESULTS: HbA1c was significantly reduced from 9.5 +/- 1.7% to 8.6 +/- 1.2% at 3 months (p < 0.03), and at 6 months 8.8 +/- 1.5% (p < 0.05). The mean daily values of blood glucose, as well as individual mean values of blood glucose at fasting and before lunch, also exhibited a significant reduction (p < 0.05) at 3 and 6 months. There was a significant reduction in the number of hypoglycemic events (level of plasma glucose <3.3 mmol/l, calculated as number of events per patient/30 days) at 3 months (6.5 +/- 5.5 vs 2.8 +/- 3.3; p = 0.02) and at 6 months (6.5 +/- 5.5 vs 3.5 +/- 3.0; p = 0.04). The insulin requirement dropped by 27.2% (1.03 +/- 0.30 U/kg/day before starting CSII; 0.75 +/- 020 U/kg/day on insulin pump therapy onset; 0.76 +/- 0.18 U/kg/day at 3 months; 0.75 +/- 0.21 U/kg/day at 6 months). During the follow-up 0.10 events of diabetic ketoacidosis/patient/year were recorded. The patients exhibited no increase in BMI during the 6 months of follow-up. CONCLUSION: CSII was safe and effective in improving short- and medium-term metabolic control in young adults, adolescents and younger children with DM.     

Response of circulating ghrelin levels to insulin therapy in children with newly diagnosed type 1 diabetes mellitus

Ghrelin is secreted primarily by the stomach, although other tissues such as the pancreas synthesize a minor proportion. The discovery of a new cell type that produces ghrelin in the human pancreas and that this organ expresses GHS-R opens new perspectives in the understanding of the control of glucose metabolism. We have studied 22 children with newly diagnosed type 1 diabetes mellitus at four different points: at diagnosis before insulin therapy, after 48-60 h of insulin therapy, and after 1 and 4 mo of insulin treatment. At each point circulating levels of ghrelin, leptin, IGF-I, IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, and glucose were determined. Ghrelin levels were significantly decreased at diagnosis (573 +/- 68 pg/mL, p < 0.01) compared with controls (867 +/- 38 pg/mL) and remained decreased after insulin therapy (d 2: 595 +/- 68 pg/mL; 1 mo: 590 +/- 61 pg/mL; 4 mo: 538 +/- 67 pg/mL) with no differences before or after insulin treatment. There was a negative correlation between ghrelin levels and body mass index at all of the study points, whereas a negative correlation between ghrelin and glucose concentrations was only observed after insulin therapy. No correlation between ghrelin and HbA1c was found at any point. A positive correlation between ghrelin and IGFBP-1 was found after insulin therapy, but no correlation with other members of the IGF system or leptin was found. In conclusion, these data could indicate a possible link between glucose concentrations and ghrelin; hence, the persisting low ghrelin levels in diabetic children may suggest a defensive mechanism against hyperglycemia.     

The role of diabetes duration, pubertal development and metabolic control in growth in children with type 1 diabetes mellitus

OBJECTIVE: To investigate whether pubertal development, duration of type 1 diabetes mellitus (DM1), or metabolic control play some role in the anomalies in growth observed in diabetic children. PATIENTS: We conducted a prospective evaluation of 83 patients (37 female, 46 male) who were followed from the onset of DM1 at the prepubertal stage until they reached final height. All patients were treated with a conventional regimen of insulin. METHODS: Height SDS, weight SDS, BMI SDS, duration of DM1 in years, and values of HbA1c were the study variables. RESULTS: In prepubertal (P1) girls (data for the initial vs the intermediate evaluations): weight SDS was -0.14 +/- 0.19 vs 0.11 +/- 0.20, p = ns; BMI SDS -0.25 +/- 0.15 vs 0.01 +/- 0.13, p = ns. In postpubertal (P3) girls, weight SDS was 0.49 +/- 0.2 vs 1.2 +/- 0.32, p <0.01; BMI SDS 0.09 +/- 0.16 vs 1.03 +/- 0.24, p <0.01, whereas in P1 boys, height SDS was 0.16 +/- 0.30 vs -0.20 +/- 0.27, p <0.05; and in P3 boys: 0.09 +/- 0.21 vs -0.28 +/- 0.26, p <0.05. Thus pubertal development influenced changes observed in girls with DM1, but did not do so in boys. The anomalies described in children with DM1 were observed from the third year of DM1 duration in both girls and boys. We did not observe any correlation between HbA1c values with height SDS, weight SDS or BMI SDS. CONCLUSIONS: The anomalies in growth observed in girls with DM1 are related to pubertal development, but this is not the case in boys. Alterations in children with DM1 were found from the third year of DM1 duration. Furthermore, the present data also indicate that the degree of metabolic control observed in our patients treated with modern but conventional regimen did not play a major role in the anomalies observed.     

Effects of TRH administration on plasma leptin levels in infants, children and adolescents

The aim of this study was to investigate the effect of thyrotropin-releasing hormone (TRH) administration (standard TRH stimulation test) on plasma leptin levels in infants, children and adolescents. Plasma leptin levels were analyzed with regard to age, body mass index (BMI) and results in standard TRH stimulation test. The study population consisted of 79 infants, children and adolescents (age: 4.50 [0.04-20.49] years; BMI: 16.47 [12.46-38.32] kg/m2; BMI SDS: 0.21 [-2.97 to 3.26]) (median [range]). Plasma leptin levels significantly decreased 30 minutes after TRH administration (5 microg/kg; maximum 200 microg i.v.) (p <0.0001). No correlation was found in leptin decrease when comparing the different groups with regard to age, BMI and results in the TRH stimulation test. Positive correlation was found when comparing BMI SDS to plasma leptin levels before (r = 0.74; p <0.001) and 30 minutes after TRH injection (r = 0.73; p <0.001). There was poor correlation when age of patients was compared to plasma leptin levels before (r = 0.46; p <0.05) and 30 minutes after TRH injection (r = 0.47; p <0.05). In summary, we found that TRH administration decreases plasma leptin levels in infants and adolescents independent of age, BMI and thyroid function.     

Children with coeliac disease and insulin dependent diabetes mellitus--growth, diabetes control and dietary intake

We aimed to assess the growth, diabetes control, dietary intake and compliance with a gluten-free diet in children with insulin dependent diabetes mellitus (IDDM) and coeliac disease in a major paediatric and adolescent diabetes clinic. Children with IDDM and biopsy-proven coeliac disease aged <18 years were included and compared with IDDM controls matched for age, sex and duration of diabetes. Twenty patients with coeliac disease and IDDM participated (15 female, age 7.4-17.3 yr), with two matched IDDM controls for each (age 6.9-17.4 yr). The prevalence of coeliac disease in this diabetes clinic population was 2.6%. All patients completed a 3 day food record (3DFR) and a 7 day food frequency questionnaire (FFQ) to assess dietary intake and gluten-free compliance. Diabetes control measured by HbA1c was not different between groups or compared to the overall clinic population (8.48 +/- 0.98% for coeliac patients vs 8.87 +/- 1.46 for IDDM controls vs 8.60 +/- 1.30 for overall clinic population aged 5.0-17.9 yr). Height, weight and BMI standard deviation scores were not different between coeliac patients and IDDM controls. No clinically significant differences were found in intake of energy, macronutrients or micronutrients. The proportion of energy intake from carbohydrate, protein and fat was within recommended ranges, except for a higher saturated fat intake. Only 30% of coeliac patients complied with a strict gluten-free diet, but growth parameters were unaffected by dietary compliance. Thus, we found that children and adolescents with coexisting IDDM and coeliac disease have normal growth, equivalent diabetes control and no differences in energy or nutrient intake compared to matched IDDM controls in our clinic population.     

Usefulness of the addition of metformin to insulin in pediatric patients with type 1 diabetes mellitus

BACKGROUND: The aim of this study was to evaluate the effect of metformin in addition to insulin therapy in adolescents and young adults with type 1 diabetes mellitus. METHODS: Nine patients, two males and seven females, aged 18.1 +/- 3.0 years, with type 1 diabetes mellitus were studied. They were relatively overweight with a body mass index (BMI) of 24.2 +/- 1.8 and had high levels of HbA1c at 9.5 +/- 1.2% despite high doses of insulin of 74.0 +/- 31.2 U/day. Metformin at the dose of 500-750 mg daily was administered to the patients in addition to insulin therapy for 1 year. RESULTS: HbA1c, BMI and insulin dose were compared before 1 year without metformin therapy, at baseline, and at 3, 6 and 12 months during the use of metformin in addition to insulin therapy. HbA1c lowered (8.6 +/- 1.4**, 8.4 +/- 1.3**, 8.4 +/- 1.2*%), BMI was reduced (23.9 +/- 1.7*, 23.8 +/- 1.8, 23.5 +/- 1.8*), and insulin requirement decreased (69.8 +/- 29.7*, 68.7 +/- 29.8**, 67.3 +/- 29.1**U/d) significantly after the start of metformin therapy (*P < 0.05, **P < 0.01 vs at baseline). There were no adverse events, not even lactic acidosis, during the study period. CONCLUSION: Metformin is safe and may represent a useful adjunct to the management of type 1 diabetes mellitus in adolescents and young adults who have poor glycemic control despite a large amount of insulin.     

The relationship of the levels of leptin, insulin-like growth factor-I and insulin in cord blood with birth size, ponderal index, and gender difference

In humans, serum levels of leptin correlate with total body fat in both adults and children. After collecting cord blood from 156 term neonates (82 males, 74 females; 132 AGA and 22 LGA), we measured the cord levels of leptin, insulin and IGF-I to determine the relationships between these three hormones and relationships of these hormones with birth size (birth weight and ponderal index for adiposity in newborn) and gender. The leptin and IGF-I levels were significantly higher in the LGA group (9.2+/-4.0 ng/ml and 96.1+/-34.1 ng/ml, respectively) than in the AGA group (4.8+/-3.8 ng/ml and 56.4+/-37.6 ng/ml, respectively). A significant positive correlation was observed between leptin levels and birth weight, and a weaker correlation between leptin levels and birth height. IGF-I level significantly correlated with birth weight and birth height, but there was no correlation between the levels of insulin and birth weight. There was no relationship between the levels of IGF-I, insulin and leptin. Ponderal index was higher in LGA than in AGA. A significant correlation was also observed between the levels of leptin and ponderal index, but not between the levels of insulin or IGF-I and ponderal index. The levels of leptin and ponderal index were higher in females than males despite no gender differences in gestational age and birth weight. In conclusion, our results suggest that the level of IGF-I is a useful index for fetal growth during late gestation, and the development of adipose tissue is the major determinant of fetal serum leptin levels, the production of which is not regulated by insulin or IGF-I. In addition, a gender difference with a higher level of leptin in female neonates suggests that sexual dimorphism in adipose tissue already exists in utero.     

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.     

Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants

BACKGROUND: It has been shown that leptin is present in breast milk and human mammary epithelial cells are able to synthesize leptin. It has been suggested that leptin in human milk might be involved in the regulation of postnatal nutrition and growth. AIMS: To investigate whether there is a relationship between leptin levels in human milk and weight gain in the postnatal period and to compare variations of milk-borne maternal leptin concentrations for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) infants. INFANTS AND METHODS: Forty-seven healthy lactating women aged from 17-38 years and their infants were included in the study. The infants were separated into three groups according to birth weight as SGA (n = 11), LGA (n = 14) and AGA (n = 22). All infants were fed with breast milk during the study period. Anthropometric measurements were performed on the 15th day of life and at 1, 2, and 3 months of age, and the body mass index (BMI) of the infants' mothers was calculated. Breast milk leptin levels were analyzed by radioimmunoassay. RESULTS: Breast milk leptin levels were found reduced in the SGA group and increased in the LGA group compared to the AGA group at 15 days of life (13.4 +/- 2.2, 28.5 +/- 4.4 and 18.4 +/- 2 ng/ml, respectively; p <0.05). At 1 month of age, leptin levels in breast milk were significantly lower in the LGA group than in the AGA group (15.5 +/- 4.9, 19.4 +/- 1.7 ng/ml, respectively; p<0.05). There was no difference among the three groups at 2 and 3 months of age (p>0.05). There was a positive correlation between birth Weight and breast milk leptin levels on the 15th day (r = 0.47, p = 0.001). A negative correlation was found between weight gain during the first 15 days and 1 month of life and breast milk leptin levels on the 15th day (r = -0.44, p = 0.002; r = -0.40, p = 0.005, respectively). No relationship could be determined between breast milk leptin levels and BMI of the mothers. CONCLUSION: Maternal milk of SGA, LGA and AGA infants had different leptin levels, especially during the first month of life. More rapid growth was shown in the SGA infants during the first postnatal 15 days compared to AGA and LGA infants, and human milk leptin levels were significantly reduced in the SGA group. However, LGA infants gained more weight during the second 15 days of life and breast milk leptin levels were dramatically decreased in LGA and increased in SGA infants at the end of first month of life. These findings suggest that the presence of leptin in breast milk might have a significant role in growth, appetite and regulation of nutrition in infancy, especially during the early lactation period, and the production of leptin in breast tissue by human mammary epithelial cells might be regulated physiologically according to necessity and state of the infant.     

Are growth factors and leptin involved in the pathogenesis of premature adrenarche in girls?

A transient increase in height and bone age as well as hyperinsulinism is seen in patients with premature adrenarche (PA). In addition, the weights of these patients are more than those of healthy peers. The aim of this study was to evaluate the role of leptin, IGF-I and IGFBPs in hyperandrogenemia and increased body weight observed in girls with PA. In this study, IGF-I, IGFBP-3, IGFBP-1 and leptin levels were investigated in 27 children with PA aged 5.4-8.6 years and 13 healthy children aged 5.7-8.58 years. Twenty patients were lean. The bone ages and BMIs of the children with PA were significantly higher than those of the healthy controls (p < 0.05). IGF-I (p < 0.005), IGFBP-3 (p < 0.05) and leptin (p < 0.0001) levels of lean PA girls were higher than controls. The leptin level of the obese PA girls was higher than that of the lean PA girls (p < 0.05) and controls (p < 0.0001). The IGFBP-1 level of the PA girls with and without obesity was lower than controls (p < 0.05). A negative correlation was observed between IGFBP-1 and leptin levels of the girls with PA (r = -0.64, p < 0.05). Serum leptin levels were influenced by BMI (p = 0.001), basal 17-OHP (p = 0.002) and stimulated 17-OHP (p = 0.019) in patients with PA. In conclusion, we suggest that elevated IGF-I and insulin give rise to increased adrenal androgens and leptin levels. On the other hand, both insulin and leptin cause decreased levels of IGFBP-1 in girls with PA, even if they are lean.     

rhGH替代治疗对生长激素缺乏儿童糖代谢的影响

目的探讨重组人生长激素(rhGH)替代治疗对生长激素缺乏症(GHD)儿童糖和胰岛素代谢的影响以及 GH 与糖代谢平衡之间的关系。方法对44例(男28例,女16例)4.5～16.5(10.4±2.6)岁 GHD 患儿在接受 rhGH 治疗前及治疗后每3个月检测体重指数、胰岛素样生长因子-1(IGF-1)、行口服葡萄糖耐量试验,计算稳态模型胰岛素抵抗指数。结果 (1)空腹血糖和 IGF-1在治疗3个月时即显著提高,一直持续较高水平,每个随访时间点与治疗前比较,差异均有统计学意义(F=6.81,7.31,P 均<0.01);稳态模型胰岛素抵抗指数和空腹胰岛素分别在治疗3和9个月时提高(P<0.01和 P<0.05),1年后下降,治疗1年半时与治疗前比较,差异已无统计学意义(均 P>0.05)。(2)相关分析发现,稳态模型胰岛素抵抗指数与体重指数、IGF-1和治疗持续时间显著相关(r=0.251,0.437,0.281,P 均<0.001)。二次方程曲线回归分析发现,稳态模型胰岛素抵抗指数与治疗持续时间呈近似抛物线量变关系。(3)发现2例暂时性高血糖,分别在停用 rhGH 治疗后1个月和5d 血糖恢复正常,再注射 rh GH 后,行口服葡萄糖耐量试验正常。结论 GHD 儿童接受 rhGH 治疗(尤第1年内)可增加胰岛素抵抗,极少数引起短暂糖代谢紊乱。循环 IGF-1可能参与控制胰岛素的敏感性,在 GH 与胰岛素平衡间起重要作用。有必要对所有接受 rhGH 治疗者定期监测糖代谢指标和 IGF-1水平。     

脑源性神经营养因子与新生儿出生体重的关系

目的：该文通过检测新生儿脐血脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）的水平,探讨BDNF与新生儿出生体重的关系,并对相关因素进行分析。方法：根据出生体重,将51 例足月第1胎健康新生儿分为3 组:①小于胎龄组（SGA）8例;②适于胎龄组（AGA ）31例;③大于胎龄组（LGA）12例。测量新生儿身长、体重及其母亲的身高、体重,并对脐血中BDNF、瘦素（LEP）、胰岛素（INS）、总胆固醇（TC）、甘油三酯（TG）进行检测。结果：SGA组的BDNF明显高于AGA组和大于LGA组,AGA组和LGA组中BDNF没有差异;多元逐步回归分析显示BDNF值与新生儿出生体重、体重指数存在负相关关系。LEP与BDNF不呈相关趋势（P>0.05）,INS与BDNF也不呈相关趋势（P>0.05）。INS 与LEP呈现正相关（P<0.05）。LEP与新生儿体重、产妇体重及其BMI呈正相关,而TC,TG在3组新生儿中差异无显著性。结论：BDNF是新生儿体重的重要影响因素,而且不受LEP,INS的影响。