Yvonne Roebroek

This thesis provides new insights for a better understanding of the difficulties that adolescents with severe obesity encounter regarding access to specialized care and weight loss surgery. Furthermore, it evaluates the physiological impact of severe obesity in adolescents, and the risks and challenges of (surgical) treatment in this specific age group.

The first part of this thesis focused on the healthcare landscape for adolescents with severe obesity. As with bariatric surgery in adults, the common opinion for bariatric surgery in adolescents has long been predominated by safety concerns, insufficient understanding of mechanisms and stigmatization.

Chapter 1 of this thesis revealed that Dutch general practitioners (GPs) only adhered to the national treatment guidelines for childhood obesity in 55.4% of the cases, and the vast majority of the GPs estimated that the available non-surgical treatment modalities are only sufficient in less than half of the patients. Although bariatric surgery was regarded as effective last-resort treatment, only 41.3% of the GPs would refer for surgery in case of therapy resistance to other treatment modalities. Main reasons for reluctance were uncertainty regarding complications in the long term and uncertainty regarding long-term efficacy. Chapter 2 showed that the healthcare landscape for children and adolescents with severe obesity differs significantly per country. At the time of the survey amongst pediatric surgeons, bariatric surgery in children and/or adolescents was allowed in several countries, however only few countries had established clinical guidelines regarding bariatric surgery in youngsters. Most pediatric surgeons regarded bariatric surgery as a viable option for adolescents with severe obesity and advocated for collaboration with adult bariatric surgeons in the treatment of this population. In chapter 3, the study protocol of the BAriatric Surgery In Children trial (BASIC) trial was presented: a randomized controlled trial (RCT) comparing laparoscopic adjustable gastric banding (LAGB) as addition to multidisciplinary lifestyle interventions (MLI) with only MLI as treatment of adolescents with severe obesity and not responding to earlier MLI treatment. Main outcome parameters were total weight loss and change in body mass index (BMI); secondary outcomes were metabolic and endocrine changes, cardiovascular abnormalities, quality of sleep, non-alcoholic steatohepatitis and several others. The reversibility of the LAGB formed a strong argument to decide for gastric banding over other surgical procedures, since the long-term risks and complications of other surgical procedures in adolescents had not been examined.

After finishing the inclusion phase of the BASIC trial, a unique cohort had been formed consisting of adolescents aged 14-16 years who had been suffering from severe obesity despite of various conservative treatment modalities (of which at least 12 months of MLI for each participant). The second part of this thesis showed the impact of severe obesity on specific health aspects in the total BASIC trial cohort at baseline.

Chapter 4 evaluated the presence of obstructive sleep apnea (OSA) in the BASIC trial cohort at baseline. Since (severe) obesity is a significant risk factor for developing OSA in adults, the main goal was to examine if OSA had already developed at such an early age. None of the analyzed participants had a prior diagnosis of OSA or had received treatment for it. 90% of the participants showed to have sleep-disordered breathing, 37.7% were classified as having moderate to severe OSA (defined as an apnea-hypopnea index (AHI) of 5 or more). The participants with moderate to severe OSA were slightly older than the non-OSA participants, had a higher weight (137.9 ± 23.7 vs. 123.5 ± 14.3 kg, p=0.008), and exhibited a higher BMI (46.9 ± 5.5 vs. 42.4 ± 4.3 kg/m², p=0.002) and BMI z-score (3.7 ± 0.3 vs. 3.4 ± 0.3, p=0.003). This suggests that every amount of weight loss can be beneficial, even though this cohort already finds itself at the extremes of the obesity spectrum. Significant differences in plasma triglyceride and insulin-like growth factor 1 (IGF-1) levels were also observed between participants with OSA and those without, and both BMI z-score and triglyceride levels were significantly associated with AHI.

Chapter 5 presented the prevalence and determinants of left ventricular geometrical changes in the BASIC trial cohort at baseline. Obesity is an independent risk factor for left ventricular hypertrophy (LVH), which is associated with a higher risk of cardiovascular morbidity and mortality in adults. LVH was found in 55.8% of the participants, predominantly in an eccentric form. Neither traditional anthropometric measures (including BMI) nor cardiovascular parameters (including blood pressure, lipid profile, etc.) correlated significantly with LVH, however multivariable linear regression analysis (correcting for BMI z-score, age and gender) showed that LVH was associated with a higher AHI (suggesting a pathophysiological relationship between nocturnal hypoxemia and LVH). Hypertrophy of the ventricular septum was associated with a higher AHI, insulin sensitivity and fasting insulin levels (after correction for BMI, age and gender). Early detection and treatment of these risk factors, particularly OSA, could improve cardiovascular outcomes.

The third part of this thesis focused on BASIC trial outcomes after one year of follow-up. Chapter 6 showed the results of the RCT after one year of follow-up, focusing on safety of the procedure, weight loss and change in BMI, and several metabolic parameters. After one year, the participants who underwent surgery (as additional treatment to MLI) achieved a significant and clinically relevant weight reduction of 11.2% on average, contrasting with a 1.7% weight gain in the control group (only MLI treatment). Improvements were also noted in fasting insulin, insulin sensitivity and serum triglycerides levels in the surgery group. Complications of the surgical treatment were mild and all successfully treated. Although the amount of weight loss might seem confined when compared to other studies, it must be taken into account that the BASIC trial was based on a stepped care approach in which comprehensive MLI had already been practiced over a year. This means that the observed health benefits could be assigned to the LAGB only and not (as in many other studies) to a combination of surgery and MLI. Despite concerns about bariatric surgery in adolescents, results suggest that it can be effective for those unresponsive to lifestyle changes.

In chapter 7, the changes in quality of sleep after one year of follow-up in the BASIC trial were evaluated. In comparison to the control group, a significant improvement in AHI was found in the surgery group, independently of BMI. The patients who had complete remission of OSA all underwent LAGB. There was no significant association between change in AHI and insulin sensitivity, or between change in AHI and leptin levels; although other studies have reported evidence for such associations, the sample size of the BASIC trial was assumed to be too small to correct for all potential confounders.