Testing for rare genetic causes of obesity: findings and experiences from a pediatric weight management program.

BACKGROUND: Genetic screening for youth with obesity in the absence of syndromic findings has not been part of obesity management. For children with early onset obesity, genetic screening is recommended for those having clinical features of genetic obesity syndromes (including hyperphagia). OBJECTIVES: The overarching goal of this work is to report the findings and experiences from one pediatric weight management program that implemented targeted sequencing analysis for genes known to cause rare genetic disorders of obesity. SUBJECTS/METHODS: This exploratory study evaluated youth tested over an 18-month period using a panel of 40-genes in the melanocortin 4 receptor pathway. Medical records were reviewed for demographic and visit information, including body mass index (BMI) percent of 95th percentile (%BMIp95) and two eating behaviors. RESULTS: Of 117 subjects: 51.3% were male; 53.8% Hispanic; mean age 10.2 years (SD 3.8); mean %BMIp95 157% (SD 29%). Most subjects were self- or caregiver-reported to have overeating to excess or binge eating (80.3%) and sneaking food or eating in secret (59.0%). Among analyzed genes, 72 subjects (61.5%) had at least one variant reported; 50 (42.7%) had a single variant reported; 22 (18.8%) had 2-4 variants reported; most variants were rare (<0.05% minor allele frequency [MAF]), and of uncertain significance; all variants were heterozygous. Nine subjects (7.7%) had a variant reported as PSCK1 "risk" or MC4R "likely pathogenic"; 39 (33.3%) had a Bardet-Biedl Syndrome (BBS) gene variant (4 with "pathogenic" or "likely pathogenic" variants). Therefore, 9 youth (7.7%) had gene variants previously identified as increasing risk for obesity and 4 youth (3.4%) had BBS carrier status. CONCLUSIONS: Panel testing identified rare variants of uncertain significance in most youth tested, and infrequently identified variants previously reported to increase the risk for obesity. Further research in larger cohorts is needed to understand how genetic variants influence the expression of non-syndromic obesity.

Obesity 2021: Rejecting Old Misconceptions and Embracing a New Paradigm to Improve Outcomes.

Despite the best efforts of many health care workers and increasing knowledge about the human energy regulatory system and dietary and exercise science, rates of obesity continue to rise. In the past 40 years, not a single country in the world has experienced a reduction in the prevalence of obesity. Over these same 40 years, treatment options such as medications, as well as bariatric and other surgical procedures, have continued to expand. Why then, are we not seeing more improvement in obesity outcomes? This commentary hypothesizes that it is due to a combination of factors. These factors include an individual's genetic predisposition combined with the modern obesogenic environment, an energy regulatory system that defends fat mass and fights loss, obesity not being seen as a disease state, and individual and societal weight bias. (Clin Ther. 2021;43:XXX-XXX) © 2021 Elsevier HS Journals, Inc.

Pilot Testing of a Patient Decision Aid for Adolescents with Severe Obesity in US Pediatric Weight Management Programs within the COMPASS Network.

Shared decision-making (SDM) is a best practice for delivering high-quality, patient-centered care when there are multiple options from which to choose. A patient decision aid (PDA) to promote SDM for the treatment of adolescent severe obesity was piloted among 12-17-year-olds (n = 31) from six pediatric weight management programs within the Childhood Obesity Multi Program Analysis and Study System (COMPASS). Medical providers used a brochure that described indications, risks, and benefits of intensive lifestyle management alone versus bariatric surgery plus lifestyle. Immediately after, patients/families completed a survey. Patient/family perceptions of provider effort to promote understanding of health issues, to listen to what mattered most to them, and to include what mattered most to them in choosing next steps averaged 8.6, 8.8, and 8.7, respectively (0 = no effort, 9 = every effort). Nearly all (96%) reported knowing the risks/benefits of each treatment option and feeling clear about which risks/benefits mattered most to them. Most (93%) reported having enough support/advice to make a choice, and 89% felt sure about what the best choice was. Providers largely found the PDA to be feasible and acceptable. This pilot will guide a more rigorous study to determine the PDA's effectiveness to support decision-making for adolescent severe obesity treatment.

The association between vitamin D and cardiometabolic risk factors in children: a systematic review.

The objective of this systematic review was to evaluate the association between serum 25-hydroxyvitamin D (25OHD) and cardiometabolic risk in children and the effect of vitamin D supplementation on risk. We included 35 clinical trials, cross-sectional studies, case-control studies, and cohort studies that evaluated the relationship between 25OHD and blood pressure, lipid levels, insulin/glucose metabolism, endothelial dysfunction, and arterial stiffness. One randomized clinical trial that randomized adolescents to 2000 or 400 IU/d of vitamin D and found improvement in arterial stiffness in the high-dose group and worsening in the low-dose group. One cross-sectional study found no relationship between 25OHD and endothelial dysfunction. Of 12 cross-sectional studies, 10 found an inverse association between 25OHD and systolic blood pressure, although 2 trials found no relationship. There was no consistent association between 25OHD and lipid levels or insulin/glucose metabolism. Insufficient evidence was available to conclude that vitamin D supplementation yields cardiometabolic benefit.

Building capacity for childhood obesity prevention and treatment in the medical community: call to action.

Large gaps exist in the capacity of the US medical system to participate meaningfully in childhood obesity-prevention efforts and to meet the treatment needs of obese children. Current primary care practice for the prevention and treatment of childhood obesity often varies from evidence-based recommendations. Childhood obesity specialists have partnered successfully with schools of medicine, professional societies, and other organizations to collaboratively engage with primary care providers in quality improvement for obesity prevention and treatment. This review and commentary targets 2 audiences. For childhood obesity experts and their organizational partners, methods to support change in primary practice and the evidence supporting their use are outlined. For primary care providers and non-obesity specialists, effective strategies for changing practice and the potential benefits of addressing childhood obesity systematically are discussed.