Adolescent obesity has markedly increased worldwide in both its extent and prevalence in recent decades and obesity prevention strategies are failing. As a result, effective treatment strategies are urgently needed. As behavioral and pharmacological treatment approaches have only moderate effects in severe obesity, bariatric surgery has begun to emerge as a treatment option. In this debate article, we offer arguments opposing and supporting bariatric surgery in the treatment of severe obesity in adolescents. Bariatric surgery has superior therapeutic outcomes with respect to weight loss and resolution of comorbid diseases over other existing treatments. However, long-term outcomes after bariatric surgery in adolescents are only just beginning to emerge. Furthermore, the procedures are generally considered irreversible, apart from gastric banding. Most importantly, not all adolescents seem to benefit greatly from bariatric surgery and we are not yet able to reliably identify those who stand to gain the greatest benefit. The authors agree that adolescent bariatric surgery should be offered exclusively within formal adolescent obesity programs, delivered by specialist multidisciplinary child/adolescent obesity teams, and within specialist centers, in order to optimize outcomes and minimize potential detrimental effects. Patients and their family/carers must be educated regarding the benefits and risks, potential side effects, expected changes in eating behavior and the lifelong requirement for regular medical follow-up after surgery. Before embarking upon a surgical treatment pathway in adolescents with severe obesity, it may also be beneficial to ensure compliance to treatment is demonstrated, in order to minimize the risk of nutritional deficiencies and associated potential complications.
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Barbara Wolters, Nina Lass, and Thomas Reinehr
Objective
The impact of thyroid hormones on weight loss in lifestyle interventions and on weight regain afterwards is unknown. Therefore, we studied the relationships between TSH, free triiodothyronine (fT3), free thyroxine (fT4), and weight status, as well as their changes during and after a lifestyle intervention in obese children.
Materials and methods
We evaluated the weight status as BMI–SDS in 477 obese children (mean age 10.6±2.7 years, 46% male, mean BMI 28.1±4.5 kg/m2) participating in a 1-year lifestyle intervention in a 2-year longitudinal study. Changes in BMI–SDS at 1 and 2 years were correlated with TSH, fT3, and fT4 concentrations at baseline and their changes during the intervention.
Results
A decrease in BMI–SDS during the intervention period (−0.32±0.38; P<0.001) was significantly positively associated with baseline TSH and fT3 in multiple linear regression analyses adjusted for age, sex, pubertal stage, and baseline BMI–SDS. An increase in BMI–SDS after the end of the intervention (+0.05±0.36; P=0.011) was significantly related to the decreases in TSH and fT3 during the intervention in multiple linear regression analyses adjusted for change in BMI–SDS during the intervention. In contrast to children with weight maintenance, children with weight regain after the end of the intervention demonstrated a decrease in their TSH levels (−0.1±1.6 vs +0.2±1.6 mU/l; P=0.03) and fT3 (−0.2±1.1 vs +0.3±1.6 pg/ml; P<0.001) during the intervention.
Conclusions
The decreases in TSH and fT3 concentrations during the lifestyle intervention were associated with weight regain after the intervention. Future studies should confirm that the decreases in TSH and fT3 levels associated with weight loss are related to the change in metabolism such as resting energy expenditure.
Thomas Reinehr, Michaela Kleber, and Andre Michael Toschke
Objective
Small for gestational age (SGA) children are at risk of both later obesity and metabolic syndrome (MetS). However, it is unknown whether obesity or SGA status leads to MetS in these subjects. We hypothesized that overweight children with former SGA status had more present components of the MetS than overweight children with former appropriate for gestational age (AGA) status.
Methods
We analyzed 803 overweight children (4% SGA, mean age 11±0.1 years, body mass index (BMI) 27.3±0.2, SDS-BMI 2.32±0.02) concerning blood pressure, lipids, glucose, and insulin. Oral glucose tolerance tests (oGTT) were performed in all 35 former SGA children and 147 randomly chosen former non-SGA children.
Results
After adjustment for age, sex, pubertal stage, and BMI-SDS, former SGA status was significantly related to blood pressure, triglyceride, insulin, and 2 h glucose levels in oGTT. The MetS prevalence was more than doubled in overweight former SGA subjects (40% MetS) compared with overweight former AGA subjects (17% MetS). The corresponding adjusted odds ratio was 4.08 (95% confidence interval 1.48 to 11.22) for SGA compared with AGA children.
Conclusions
Overweight former SGA children had an increased risk for the components of the MetS compared with overweight former AGA children. Therefore, SGA status seems to be a risk factor for the MetS independently of weight status. Particularly overweight children with former SGA status should be screened for the MetS.
Joachim Woelfle, Christian L Roth, Rainer Wunsch, and Thomas Reinehr
Background
Pregnancy-associated plasma protein A (PAPPA) is a large placenta-derived glycoprotein, which serves as a protease of several IGF-binding proteins (IGFBPs). In non-pregnant adults, measurable PAPPA levels were detected and have been implicated in the pathophysiology of atherosclerotic plaques. However, data in children is lacking.
Objective
To study the relationship between PAPPA, markers of atherosclerosis, and members of the IGF system in pediatric obesity.
Patients and design
Eighty-two obese and 52 nonobese children and 1-year longitudinal follow-up study for obese cohort.
Intervention
Outpatient 1-year intervention program based on exercise, behavior, and nutrition therapy.
Main outcome measures
Changes in PAPPA levels, carotid intima media thickness (IMT), weight, blood pressure, lipids, metabolic markers, and members of IGF system.
Results
Baseline PAPPA (PAPPABL) serum levels did not differ between obese and lean subjects. PAPPABL correlated significantly with IGF1, IGFBP1, and serum cholesterol. During the 1-year-program mean IMT decreased from 0.66±0.01 to 0.63±0.01 mm (P<0.05) and PAPPA from 1.83±0.12 to 1.58±0.11 μU/l (P<0.00). In linear regression analysis with IMT after intervention as dependent variable, PAPPA contributed significantly to the observed variance. The longitudinal change of PAPPA correlated significantly with the change of serum triglycerides.
Conclusion
In this cohort of obese children, PAPPA serum levels correlated significantly with other cardiovascular risk factors. The lack of a direct correlation between PAPPA and IMT suggests that the described association of atherosclerotic plaques and increased PAPPA levels might reflect an indirect mechanism of PAPPA with cardiovascular risk factors such as serum lipids rather than a direct effect on the vasculature.
Thomas Reinehr, Gideon de Sousa, Ute Alexy, M Kersting, and Werner Andler
Objective: The roles of vitamin D and parathyroid hormone (PTH) are discussed controversially in obesity, and studies of these hormones in obese children are limited. Therefore, we studied the relationships between PTH, 1,25-dihydroxy-vitamin D (1,25-OH Vit D), 25-hydroxy-vitamin D (25-OH Vit D), weight status, and insulin sensitivity before and after weight loss in obese children.
Methods: Fasting serum PTH, 1,25-OH Vit D, 25-OH Vit D, inorganic phosphate, calcium, alkaline phosphatase (AP), insulin, glucose, and weight status (SDS–BMI and percentage body fat) were determined in 133 obese children (median age 12.1 years) and compared with 23 non-obese children. Furthermore, these parameters were analyzed in 67 obese children before and after participating in a 1-year obesity intervention program.
Results: Obese children had significantly (P < 0.001) higher PTH and lower 25-OH Vit D concentrations compared with non-obese children, while calcium, phosphate, AP, and 1,25-OH Vit D did not differ significantly. Changes of PTH (r = 0.23, P = 0.031) and 25-OH Vit D (r = −0.27, P = 0.013) correlated significantly with changes of SDS–BMI, but not with changes of insulin sensitivity (homeostasis model assessment; HOMA-B%). Reduction of overweight in 35 children led to a significant (P < 0.01) decrease of PTH concentrations and an increase in 25-OH Vit D levels.
Conclusions: PTH levels were positively and 25-OH Vit D concentrations were negatively related to weight status. Since these alterations normalized after weight loss, these changes are consequences rather than causes of overweight. A relationship between PTH, vitamin D, and insulin sensitivity based on the HOMA index was not found in obese children. Further longitudinal clamp studies are neccessary to study the relationship between vitamin D and insulin sensitivity.
Susanna Wiegand, Klemens Raile, Thomas Reinehr, Sabine Hofer, Andrea Näke, Wolfgang Rabl, Reinhard W Holl, and on behalf of the DPV-Wiss Study Group
Design
The purpose of this study was to generate insulin dose (ID) percentiles for children and adolescents with type 1 diabetes mellitus (DM1) having the opportunity to assess this important parameter in relation to age and sex.
Methods
Daily IDs per weight (ID/kg) were recorded in 22 177 patients with DM1 (3–25 years of age, DM1 duration of more than 2 years, 48% female) and ID percentiles (ID-Perc) were created statistically. The ID-Perc were compared between male and female, and between multiple insulin injection therapy (MIT) and continuous s.c. insulin infusion (CSII). A multivariate regression analysis was performed for ID in the third year of DM1 with ID/kg, body weight, age, gender, and insulin delivery regimen as variables.
Results
The 50th ID-Perc (P50) varied among 0.67 IU/kg (age 3 years), 0.93 IU/kg (13 years), and 0.70 IU/kg (23 years) increasing from early childhood to adolescence and decreasing toward adulthood. Highest P50 ID was found at 12 years in females (0.94 IU/kg) and at 14 years in males (0.92 IU/kg). Using ICT, the ID was significantly higher compared with CSII (P50: 0.94 IU/kg versus 0.79 IU/kg at 13 years). In multivariate regression analysis, ID was significantly (P>0.001) associated with age, gender, and insulin delivery regime.
Conclusion
The ID-Perc were significantly different during various periods of childhood and were influenced by gender, body weight, and insulin injection regimes. Therefore, the presented data 1) provide evidence to interpret individual ID in children and adolescents with DM1 and 2) more specifically identify children with unusually high (insulin resistance and non-compliance) or low (MODY and persistent remission) insulin requirement.