Medicine & Dentistry-Pediatrics
University of Alberta
Summary of research:
1. Autonomic nervous system activity and metabolic profiling in children with Prader-Willi Syndrome compared to controls Prader-Willi Syndrome (PWS) is the most common genetic form of childhood obesity, affecting over 3000 Canadians. Children with PWS suffer from a constant feeling of hunger that results in overeating and weight gain. However, some studies indicate that obese PWS children may have a lower risk of developing obesity-related diseases (type II diabetes),than obese children without PWS. One factor that might contribute to differences between obese children with and without PWS is autonomic nervous system (ANS) function. The ANS controls essential functions like breathing, heart rate, digestion, body temperature and level of hormones. Some characteristics of PWS (low blood sugar, abnormal sleep, body temperature instability, reduced pain sensitivity, learning disabilities and sudden death) indicate impaired ANS function. However, ANS function has not been well-characterized in children with PWS. ANS function also may be related to risk factors for the development of obesity-related disease such as control of blood sugar levels and where body fat is located in the body. Therefore, we propose to answer the following questions: A. What are the specific characteristics of ANS dysfunction in PWS? B. How does ANS function in PWS differ compared to children without PWS? C. Are differences in ANS activity associated with the amount of total body fat, fat stored in the abdomen and glucose levels in PWS? We will answer these questions by measuring ANS function, total body fat and body fat in the abdomen and hormone levels in children with PWS, and compare the results to children without PWS. Identification of the specific ANS dysfunction in children with PWS could lead to the development of new therapies for PWS that address several of the clinical manifestations which lower quality of life (constant hunger, sleep disturbances, and learning disabilities). Lastly, this study will improve our understanding about the role of the ANS in general childhood obesity. 2.Dietary intake of Children with Prader-Willi Syndrome Prader-Willi Syndrome (PWS) is a genetic disorder that occurs in approximately 1 out of every 10, 000 births. During infancy, PWS is characterized by low muscle tone and failure to thrive. The second phase of PWS includes the development of an insatiable appetite in early childhood, which can lead to hyperphagia and excessive weight gain if energy intake is not controlled. Since children with PWS have relatively low energy requirements, meeting nutrient recommendations requires an emphasis on nutrient dense foods. The study objective is to compare micro- and macronutrient intake of children with PWS, ages 5-17 years, with controls and to evaluate the diet quality of all subjects. Twenty-two children with PWS and 11 controls were previously recruited to assess the efficacy of the project. We will now aim to recruit an additional 40 subjects (20 PWS and 20 controls) to ensure an adequate sample size and a dietary intake that is representative of the Canadian population. Three-day dietary records will be obtained from each subject and will be analyzed using Food Processor software. Micro- and macronutrient intake of the children with PWS will be compared to current nutrient recommendations, as well as to the nutrient intake of children without PWS. Diet quality will also be assessed using the Healthy Eating Index Canada-2009 (HEIC-2009) and Healthy Eating Index Canada (HEIC). We expect that despite consuming a diet that is considered high quality, children with PWS will be at risk for deficiencies in several nutrients including vitamin D, calcium and iron. 3. Evidence-based approach to dietary management of Prader-Willi Syndrome Prader-Willi Syndrome (PWS) is a genetic disease characterized by failure to thrive and low muscle tone during infancy, followed by food-seeking, insatiable appetite and progressive obesity in childhood. The resulting increases in total body fat and decreases in muscle mass lead to metabolic problems such as diabetes and heart disease. Several diets are recommended for the management of body weight in individuals with PWS such as the Red-Yellow-Green system which is a low-fat, low calorie diet. However, none of the recommended diets have been scientifically proven to benefit individuals with PWS. Additionally, attempts to control weight and prevent food-seeking have variable success in PWS because the underlying basis for their food-seeking and the optimal dietary composition of nutrients such as carbohydrate, fat and protein for metabolic control in PWS remains to be determined. We propose a detailed, cutting-edge study that will assess a wide array of metabolites (“metabolomics” study) in many important metabolic pathways in PWS in response to intake of varying diets (low carbohydrate versus low fat). We will also assess measures of appetite and hunger before and after each different diet. Our previous studies have shown that the excessive food seeking in PWS may be triggered or maintained by an increase in levels of an appetite-stimulating hormone called ghrelin. We therefore propose that studies of the nutrient regulation of ghrelin will provide guidance in the design of effective diets for PWS based on scientific evidence. Information obtained from this study will be used to design evidence-based diet plans for children with PWS. Results of this study also may benefit children with other genetic obesity conditions.