Pernilla Danielsson

Response of Severely Obese Children and Adolescents to Behavioral Treatment

OBJECTIVES To investigate whether the degree of obesity predicts the efficacy of long-term behavioral treatment and to explore any interaction with age. DESIGN A 3-year longitudinal observational study. Obese children were divided into 3 age groups (6-9, 10-13, and 14-16 years) and also into 2 groups (moderately obese, with a body mass index [BMI]-standard deviation [SD] score [or z score] of 1.6 to <3.5, and severely obese, with a BMI-SD score of ≥3.5). SETTING National Childhood Obesity Center, Stockholm, Sweden. PARTICIPANTS Children 6 to 16 years of age who started treatment between 1998 and 2006. INTERVENTION Behavioral treatment of obesity. MAIN OUTCOME MEASURE Change in BMI-SD score during 3 years of treatment; a reduction in BMI-SD score of 0.5 units or more was defined as clinically significant. RESULTS A total of 643 children (49% female children) met the inclusion criteria. Among the youngest moderately obese children, 44% had a clinically significant reduction in BMI-SD score (mean reduction, -0.4 [95% CI, -0.55 to -0.32]). Treatment was less effective for the older moderately obese children. Twenty percent of children who were 10 to 13 years of age and 8% of children who were 14 to 16 years of age had a reduction in BMI-SD score of 0.5 units or more; 58% of the severely obese young children showed a clinically significant reduction in BMI-SD score (mean reduction, -0.7 [95% CI, -0.80 to -0.54]). The severely obese adolescents showed no change in mean BMI-SD score after 3 years, and 2% experienced clinically significant weight loss. Age was found to be a predictor of a reduction in BMI-SD score (odds ratio, 0.68 units per year [95% CI, 0.60-0.77 units per year]). CONCLUSIONS Behavioral treatment was successful for severely obese children but had almost no effect on severely obese adolescents.

Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes

Recent studies have shown that SNPs in the FTO gene predispose to childhood and adult obesity. In this study, we examined the association between variants in FTO and KIAA1005, a gene that maps closely to FTO, and obesity, as well as obesity related traits among 450 well characterised severely obese children and 512 normal weight controls. FTO showed significant association with several obesity related traits while SNPs in KIAA1005 did not. When stratified by gender, the FTO variant rs9939609 showed association with obesity and BMI among girls (P=0.006 and 0.004, respectively) but not among boys. Gender differences were also found in the associations of the FTO rs9939609 with obesity related traits such as insulin sensitivity and plasma glucose. This study suggests that FTO may have an important role for gender specific development of severe obesity and insulin resistance in children.

Orlistat treatment in obese prepubertal children: a pilot study

Aim: This study investigated orlistat treatment in obese prepubertal children with regard to tolerance, safety and psychological well‐being. Methods: 11 healthy, severely obese prepubertal children (age 8.3–12.3 y, body mass index standard deviation score 5.3–9.2) were recruited for a 12wk open treatment. Before, during and after treatment, the participants were investigated by psychological evaluation, blood chemistry, and parameters reflecting obesity and fat mass. Results: The participants were able to comply with the treatment, as indicated by pill counts and self reports, and expressed a desire to continue the treatment after the study period. Gastrointestinal side effects were mild and tolerable. No negative effects on psychological or physical well‐being were detected, and the psychological evaluation demonstrated increased avoidance of fattening food, body shape preoccupation and oral control (p= 0.011). The median weight loss was 4.0 kg (range –12.7 to +2.5 kg, p= 0.016) and was highly correlated to decreased fat mass (regression coefficient 0.953, p < 0.01).

Associations between severity of obesity in childhood and adolescence, obesity onset and parental BMI: a longitudinal cohort study

Objective:To explore the relationship between severity of obesity at age 7 and age 15, age at onset of obesity, and parental body mass index (BMI) in obese children and adolescents.Design:Longitudinal cohort study.Subjects:Obese children (n=231) and their parents (n=462) from the Swedish National Childhood Obesity Centre.Methods:Multivariate regression analyses were applied with severity of obesity (BMI standard deviation score (BMI SDS)) and onset of obesity as dependent variables. The effect of parental BMI was evaluated and in the final models adjusted for gender, parental education, age at onset of obesity, severity of obesity at age 7 and obesity treatment.Results:For severity of obesity at age 7, a positive correlation with maternal BMI was indicated (P=0.05). Severity of obesity at this age also showed a strong negative correlation with the age at onset of obesity. Severity of obesity at age 15 was significantly correlated with both maternal and paternal BMI (P<0.01). In addition, BMI SDS at age 15 differed by gender (higher for boys) and was positively correlated with severity of obesity at age 7 and negatively correlated with treatment. Also, a negative correlation was indicated at this age for parental education. No correlation with age at onset was found at age 15. For age at onset of obesity there was no relevant correlation with parental BMI. Children within the highest tertile of the BMI SDS range were more likely to have two obese parents.Conclusion:The impact of parental BMI on the severity of obesity in children is strengthened as the child grows into adolescence, whereas the age at onset is probably of less importance than previously thought. The influence of parental relative weight primarily affects the severity of childhood obesity and not the timing.

Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents

Background:The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits.Results:We screened exons 3 and 4 including exon–intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768–1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS.Conclusion:These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.

Importance of Age for 3-Year Continuous Behavioral Obesity Treatment Success and Dropout Rate

Objective: To assess whether first year weight loss, age, and socioeconomic background correlate with the success rate of continuous long-term behavioral obesity treatment. Methods: In a 3-year longitudinal study, obese children (n = 684) were divided into three groups based on age at the start of treatment, age 6–9 years, 10–13 years, and 14–16 years. Results: The mean BMI standard deviation score (BMI-SDS) decline was age-dependent (p = 0.001), independently of adjustment for missing data: –1.8 BMI-SDS units in the youngest, –1.3 in the middle age group, and –0.5 in the oldest age group. SES and parental BMI status did not affect the results. 30% of the adolescents remained in treatment at year 3. There was only a weak correlation between BMI-SDS change after 1 and 3 years: r = 0.51 (p < 0.001). Among children with no BMI-SDS reduction during year 1 (n = 46), 40% had a clinically significantly reduced BMI-SDS after year 3. Conclusion: Behavioral treatment should be initiated at an early age to increase the chance for good results. Childhood obesity treatment should be continued for at least 3 years, regardless of the initial change in BMI-SDS.

Genetic variance in the adiponutrin gene family and childhood obesity.

Aim The adiponutrin gene family consists of five genes (PNPLA1-5) coding for proteins with both lipolytic and lipogenic properties. PNPLA3 has previously been associated with adult obesity. Here we investigated the possible association between genetic variants in these genes and childhood and adolescent obesity. Methods/Results Polymorphisms in the five genes of the adiponutrin gene family were selected and genotyped using the Sequenom platform in a childhood and adolescent obesity case-control study. Six variants in PNPLA1 showed association with obesity (rs9380559, rs12212459, rs1467912, rs4713951, rs10947600, and rs12199580, p<0.05 after adjustment for age and gender). Three variants in PNPLA3 showed association with obesity before, but not after, adjustment for age and gender (rs139051, rs12483959, and rs2072907, p>0.05). When analyzing these SNPs in relation to phenotypes, two SNPs in the PNPLA3 gene showed association with insulin sensitivity (rs12483959: β = −0.053, p = 0.016, and rs2072907: β = −0.049, p = 0.024). No associations were seen for PNPLA2, PNPLA4, and PNPLA5. Conclusions Genetic variation in the adiponutrin gene family does not seem to contribute strongly to obesity in children and adolescents. PNPLA1 exhibited a modest effect on obesity and PNPLA3 on insulin sensitivity. These data, however, require confirmation in other cohorts and ethnic groups.

Interaction between PPARG Pro12Ala and ADIPOQ G276T concerning cholesterol levels in childhood obesity

AIM The aim of this study was to investigate the role of two candidate gene polymorphisms for insulin resistance and lipid levels in obese children and adolescents. METHODS Two markers of insulin resistance and lipid levels, Pro12Ala in peroxisome proliferator-activated receptor-gamma2 (PPARG) and G276T in adiponectin (ADIPOQ), were genotyped in 285 obese children and adolescents. As the apolipoprotein E (APOE) polymorphisms C112R and R158C are known to have a profound impact on lipid levels in both children and adults, results were adjusted for APOE genotype. RESULTS We found no association for PPARG or ADIPOQ polymorphisms with Body Mass Index (BMI), High Density Lipoprotein (HDL)-cholesterol, triglycerides or Insulin Resistance estimated by Homeostasis Model of Assessment (HOMA-IR). Wild type carriers of PPARG Pro12Ala (p<0.05), homozygous carriers of the variant allele of ADIPOQ G276T (p<0.001) and epsilon4 carriers of APOE (p<0.001) had higher total and low density lipoprotein (LDL)-cholesterol levels adjusted for age, gender, BMI and insulin sensitivity. A PPARG/ADIPOQ risk genotype combination was identified by analysis of covariance (ANCOVA) comparing all existing combinations. Carriers of PPARG Pro/Pro and ADIPOQ 276 T/T had higher total (5.0 [4.1-5.8] vs. 4.1 [3.6-4.6] mmol/l) and LDL-cholesterol levels (3.7 [2.9-4.5] vs. 3.0 [2.5-3.5] mmol/l) compared with carriers of other combinations (p<0.001). Importantly, the PPARG and ADIPOQ associations were unaffected when adjusting for APOE genotype. CONCLUSIONS Genetic variants in candidate genes for insulin resistance are associated with cholesterol levels in obese children and adolescents, and may offer additional information in the risk assessment of obese children.

Five-year outpatient programme that provided children with continuous behavioural obesity treatment enjoyed high success rate.

Results from long‐time follow‐up of obesity treatment in early childhood are lacking. We investigate long‐term continuous behavioural childhood obesity treatment and factors of importance for treatment effect.

Blood sugar levels are higher in obese young children in Sweden than in Poland

An elevated fasting glucose level is an early sign of metabolic dysfunction in obese children. This study compared fasting glucose levels in obese young children in Poland and Sweden.