Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program.

BACKGROUND: It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic improvements during weight loss is uncertain. OBJECTIVE: The objective was to prospectively examine associations between plasma leptin, body fat, and weight and metabolic risk factors in obese children during weight loss. DESIGN: In obese children and adolescents [n = 203; mean age: 14.1 y, >98th body mass index (BMI) percentile for age and sex] participating in a 2-mo inpatient weight-loss program, we measured changes in body composition (by dual-energy X-ray absorptiometry), plasma leptin, insulin, and lipids. After discharge, anthropometric measures and plasma leptin were remeasured at 6 (n = 139) and 12 (n = 100) mo. RESULTS: During the 2-mo program, mean (±SD) weight and fat loss were 13.9 ± 4.0 kg and 9.2 ± 2.5 kg, respectively; and mean plasma leptin decreased by 76%. Weight and fat loss were sustained, and no significant differences in BMI-SD score (SDS) or body composition were found between 12 and 2 mo. Baseline leptin was a negative predictor for percentage fat loss at 2, 6, and 12 mo (P < 0.05). The percentage change in leptin during the 2-mo intervention positively correlated with the relative change in fasting insulin, the relative change in LDL cholesterol at 2 mo, percentage fat loss, and change in BMI-SDS at 2 and 6 mo (P < 0.02). CONCLUSIONS: Even in obese children with strongly elevated baseline leptin, large leptin reductions that predict short- and long-term loss of body fat and improvements in lipids and insulin sensitivity can be achieved. Thus, increased plasma leptin in obese children may not necessarily reflect leptin resistance; many children appear to remain leptin sensitive at this age.

During rapid weight loss in obese children, reductions in TSH predict improvements in insulin sensitivity independent of changes in body weight or fat.

BACKGROUND: Although serum TSH is often elevated in obesity and may be linked to disorders of lipid and glucose metabolism, the clinical relevance of these relationships remains unclear. SUBJECTS: Subjects were obese children and adolescents (n=206; mean age 14 yr) undergoing rapid weight and fat loss in a standardized, multidisciplinary, 2-month, in-patient weight loss program. DESIGN: This was a prospective study that determined thyroid function, glucose and lipid parameters, leptin, anthropometric measures, and body composition measured by dual-energy x-ray absorption at baseline and at the end of the intervention. RESULTS: At baseline, 52% of children had TSH concentrations in the high normal range (>2.5 mU/liter), but TSH was not correlated with body weight, body mass index sd scores, lean body mass, or body fat percentage. At baseline, independent of adiposity, TSH significantly correlated with total cholesterol (P=0.008), low-density lipoprotein cholesterol (P=0.013), fasting insulin (P=0.010), homeostatic model assessment (HOMA) (P=0.004), and leptin (P=0.006). During the intervention, mean body fat, TSH, HOMA, and fasting insulin decreased by 21, 11, 53, and 54%, respectively. Change (Δ) in TSH did not correlate with Δbody weight or Δbody composition, but ΔTSH significantly correlated with, Δfasting insulin and ΔHOMA, independent of Δbody weight or Δbody composition (P<0.05). CONCLUSION: TSH concentrations are elevated in obese children but are not correlated with the amount of excess body weight or fat. During weight loss, independent of changes in body weight or composition, decreases in elevated serum TSH predict decreases in fasting insulin and HOMA. These findings suggest interventions that target high TSH concentrations during weight loss in obese subjects may improve insulin sensitivity.

Effects of a multidisciplinary inpatient intervention on body composition, aerobic fitness, and quality of life in severely obese girls and boys.

PURPOSE: The last few decades have seen a major increase in the prevalence of juvenile obesity. Inpatient treatment programs are used mainly in children with severe obesity and related comorbidities. The aim of this study was to evaluate the gender differences of an 8-week multidisciplinary inpatient program on body weight, body composition, aerobic fitness, and quality of life of severely obese children and adolescents. METHODS: Body weight was measured daily, and body composition, aerobic fitness, and quality of life were measured at the beginning and the end of an 8-week multidisciplinary inpatient program in 130 severely obese patients (52 girls, 78 boys), median (25th, 75th percentile) age of 13.8 (12.1, 15.0) years, median body weight of 89.4 kg (77.1, 100.1), and a body mass index of 33.4 (30.1, 36.6) kg/m(2), which is well above the 98th percentile. The inpatient program was based on a multidisciplinary treatment and education program that focused on daily physical activity, a 1200-1600 kcal/day balanced nutrition regimen, and a behavior modification therapy. RESULTS: All results are expressed as medians (25th, 75th percentiles). At the end of the program all patients had lost a significant amount of body weight: 12.7 kg (10.8, 16.6), p < .001, girls 11.6 kg (9.7, 13.2), boys 13.7 kg (11.7, 17.3), p < .001, absolute body fat 8.0 kg (6.8, 10.0) p < 001, girls 7.0 kg (5.7, 8.1), boys 9.4 kg (7.6, 11.0) p < .001, % body fat per kg body weight: 4.9% (3.2, 6.6) p < .001, girls 3.7% (2.7, 4.9), boys 5.7% (4.0, 7.5) p < .001, and absolute fat free (or lean body) mass: 1.8 kg (0.64, 3.0) p < .001, girls 1.8 kg (0.87, 3.2), boys 1.7 kg (0.50, 2.9) p = .43. In addition, all measurements of aerobic fitness: VO(2)peak (mL/min.kg) and peak mechanical power (watts and watt/kg) and of quality of life increased significantly (p < .001, p < .001, p < .004 to p < .001). CONCLUSION: A multidisciplinary inpatient treatment program including moderate calorie restriction, daily physical activity, and behavior modification induced a major weight loss, a decrease in body fat, and an increse in aerobic fitness as well as the quality fo life of severely obese children and adolescents. Weight loss and the decrease in body fat (absolute and percent) were significantly more pronounced in boys than girls.

High incidence of exercise-induced bronchoconstriction in triathletes of the Swiss national team.

AIM: To assess the progression of bronchial reactivity (BR) and incidence of bronchial hyperreactivity (BH), exercise-induced bronchoconstriction (EIB) and asthma in triathletes over 2 years. METHODS: Subjects were seven athletes from the Swiss national triathlon team (mean (SD) age 24.3 (4.8) years), who initially were not asthmatic, not treated with antiasthmatic medication, and who had performed at international level for more than 3 consecutive years (2001-2003). To assess BR, BH and EIB, subjects ran on a 400 m track for 8 min at intensities equal to the anaerobic threshold. Tests were conducted in ambient temperatures of 4.4 (2.8) degrees C, -8.8 (2.4) degrees C and 3.6 (1.5) degrees C, and humidity of 52 (16)%, 83 (13)% and 93 (2)%. Forced expiratory volume in 1 s (FEV(1)) was measured before and at 2, 5, 10 and 15 min after EIB, and 5 min after inhalation of a beta2 agonist. Two methods were used to calculate the incidence: (1) the standard assessment; (2) extrapolation of the decrease in FEV(1) to the BH limit. RESULTS: BR increased significantly in the seven athletes (FEV(1): year, p = 0.04; year x EIB, p = 0.002; EIB p<0.001). Within 2 years, BR had increased significantly and even reached BH in some athletes. Three athletes exhibited BH. After extrapolation of the decrease in FEV(1) in all seven athletes, the limit of 10% by definition for BH was determined to occur within 1.77-4.81 years, resulting in 21-57% of athletes with newly developed BH per year. CONCLUSION: Athletes develop EIB quickly, a rate of increase 195-286 times that of the normal rate for development of asthma.

Effect of ipratropium bromide on EIB in children depends on vagal activity.

PURPOSE: Ipratropium bromide (IB) has been used to prevent exercise-induced bronchoconstriction (EIB), but its effect varies among individuals. We hypothesized that such variability may reflect individual differences in vagal activity (VA), and therefore determined whether a correlation exists between VA and the effect of IB on EIB in 13.0 (+/-0.8)-yr-old children with asthma and documented EIB. METHODS: Subjects served as their own control and were tested on three occasions in an ambient temperature of 5 degrees C. Visit I included no treatment. In visits II and III (counterbalanced sequence) subjects inhaled either 500 microg IB or 0.9% NaCl as a placebo, 45 min before exercise provocation. Investigators and the subjects were blinded to the inhaled substance. VA was assessed by a 4-s exercise test (3). The ratio of resting ECG R-R-interval at full inspiration to the lowest R-R interval during 4-s cycling was taken as an index of VA. Eight-minute cycling at constant work rate (HR=173+/-4 bpm) at 5 degrees C was used to provoke EIB. A two-factor (treatment x time) repeated-measures ANOVA was used. RESULTS: The exercise-induced drop in FEV1 was similar in the three sessions. However, because the IB caused a 15.7+/-4.1 increase in FEV1 preexercise, the postexercise values after a placebo or no treatment were consistently lower than after IB. The beneficial response to IB, compared with no treatment and with placebo, was positively correlated to VA (for FEV1: r=0.91, P=0.002; and r=0.90, P=0.002, respectively). CONCLUSION: We suggest that the therapeutic effect of IB on exercise-induced asthma may be related to vagal activity.

Facial cooling enhances exercise-induced bronchoconstriction in asthmatic children.

PURPOSE: Exercising in cold air enhances bronchial responsiveness (BR) as compared with exercising in warm air. This may be due to intrathoracic cooling or to increased vagal activity caused by facial cooling. The purpose of this study was to compare the effects on BR of cold air inhalation and of facial exposure to cold air, as well as the combined effect of both. METHODS: Fourteen children with asthma (eight girls) performed four exercise challenge tests in a climatic chamber, under one of the following conditions: 1) inhaling warm air while the face was exposed to warm air (WW, 21 degrees C, 25% relative humidity (RH)); 2) inhaling warm air while the face was exposed to cold air (WC, 0 degrees C, 80% RH); 3) inhaling cold air while the face was exposed to cold air (CC); and 4) inhaling cold air while the face was exposed to warm air (CW). The study was analyzed, using a one- and two-way ANOVA. RESULTS: Postexercise forced expiratory volume in the first second (FEV1) and maximal mid-expiratory flow (MMEF) values as percent predicted (% pred) showed significant reductions over time (P < 0.001), significant differences among the four experimental conditions (P < 0.001) and a significant condition x time interaction (FEV1:P < 0.001, MMEF:P < 0.01). FEV1 was significantly lower for CC and WC, as compared with WW and CW at 5 and 10 min postexercise. The lowest postexercise values for FEV1 occurred in the CC and WC sessions (76% predicted in both). A similar pattern was obtained for MMEF. CONCLUSION: Facial cooling combined with either cold or warm air inhalation causes the greatest EIB, as compared with the isolated challenge with cold air inhalation. We suggest that vagal mechanisms play a major role in exercise and cold-induced bronchoconstriction.