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
Murer, S.B. ; Knopfli, B.H. ; Aeberli, I. ; Jung, A. ; Wildhaber, J. ; Wildhaber-Brooks, J. ; Zimmermann, M.B. - \ 2011
American Journal of Clinical Nutrition 93 (2011)4. - ISSN 0002-9165 - p. 695 - 702.
blood-brain-barrier - serum leptin - body-weight - insulin-resistance - loss maintenance - plasma leptin - overweight - adiposity - life - intervention
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
Aeberli, I. ; Jung, A. ; Murer, S.B. ; Wildhaber, J. ; Wildhaber-Brooks, J. ; Knopfli, B.H. ; Zimmermann, M.B. - \ 2010
Journal of Clinical Endocrinology and Metabolism 95 (2010)12. - ISSN 0021-972X - p. 5412 - 5418.
coronary-heart-disease - subclinical hypothyroidism - thyroid-function - reference range - morbid-obesity - in-vivo - leptin - risk - adolescents - population
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 (Delta) in TSH did not correlate with Delta body weight or Delta body composition, but Delta TSH significantly correlated with, Delta fasting insulin and Delta HOMA, independent of Delta body weight or Delta body 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. (J Clin Endocrinol Metab 95: 5412-5418, 2010)