Dr Bacha’s laboratory at the Children’s Nutrition research Center (CNRC) investigates the risk factors and mechanisms underlying the pathogenesis of the metabolic complications related to childhood obesity and insulin resistance with a focus on youth-onset type 2 diabetes, cardiovascular disease risk and subclinical atherosclerosis. Her lab utilizes state of the art methodology to understand the pathophysiology of these nutrition related diseases in children and adolescents, so that more targeted prevention and intervention strategies can be implemented.
Glucose and Insulin Metabolism- Prediabetes and Type 2 Diabetes in Youth
Earlier work by Dr. Bacha focused on understanding the relationship of adiposity to insulin resistance and characterizing the risk factors for type 2 diabetes in youth. Her work on the pathophysiological mechanisms of prediabetes and type 2 diabetes contributed to the current understanding of the pathophysiology of the disease in children, and the importance of the defect in beta cell function to the pathogenesis and the rapid progression of type 2 diabetes and its complications in childhood. Dr. Bacha has been a longterm investigator in the TODAY study and its long-term post-intervention follow-up TODAY 2. This project investigated the natural history of type 2 diabetes in children, therapeutic options and longitudinal follow-up post participation in the study.
Currently Dr. Bacha’s laboratory is pursuing the use metabolomics to uncover biomarkers of beta cell function and cardiovascular disease in youth with type 2 diabetes.
A new study aims to characterize the pathogenesis of youth-onset prediabetes and type 2 diabetes to better identify youth at risk for the disease.
Endothelial Dysfunction and Subclinical Atherosclerosis:
Dr Bacha’s work aimed to delineate the cardiovascular complications related to childhood obesity, insulin resistance and type 2 diabetes, and to identify adequate biomarkers of subclinical atherosclerosis in youth, and their determining factors. She utilized different methodologies to measure vascular function including pulse wave velocity and intima media thickness, and coronary artery calcifications (CAC), as early biomarkers of subclinical atherosclerosis. Her work demonstrated that different aspects of subclinical atherosclerosis appear to be differentially modulated, adiposity being the major determinant of CAC, hyperglycemia for intima media thickness, and leptin and insulin sensitivity for arterial stiffness. She also demonstrated that peripheral endothelial function is a biomarker of vascular health modulated by insulin sensitivity in youth. In addition, work in her lab showed that non-alcoholic fatty liver disease in youth is associated with multi-organ insulin resistance and significant endothelial dysfunction directly related to the hepatic fat content. This was independent of visceral adiposity or glycemia. Ongoing work is focusing on understanding thee determinants of cardiac autonomic dysfunction in youth across the glycemic spectrum.
In the TODAY study, she also described evidence of early cardiac injury in relation to obesity and high blood pressure in youth-onset type 2 diabetes and contributed to work showing rapid progression of cardiovascular disease risk in youth with type 2 diabetes.
A recent project aims to understand the role of the advanced glycation endproducts (AGEs), and their receptor as biomarkers of microvascular and macrovascular disease in youth-onset type 2 diabetes.
Sleep, Circadian Dysregulation and Energy Metabolism
Her work included evaluation of the perturbations in energy metabolism related to obesity across the glycemia spectrum in youth, and the relationship of sleep dysfunction and circadian dysregulation to energy homeostasis and glucose metabolism in children. She showed reduced metabolic flexibility in the setting of severe insulin resistance in youth across the glycemic spectrum (JCI Insights 2021). She also investigated the relationship of sleep parameters (actigraphy) to physical activity and energy metabolism. These studies showed that delayed sleep timing is an important factor in determining physical activity in children. Reduced sleep duration was related to increased sedentary behaviors and less time spent in light physical activity. Moreover, she utilized indirect calorimetry and the doubly labelled water measures of energy expenditure, and showed that shorter sleep duration was associated with lower basal metabolic rate after accounting for age, sex, fat mass and lean mass.
Bone Health
A new area of investigation in the Bacha laboratory focuses on Bone Health in Children. She is utilizing high resolution peripheral quantitative computed tomography (HRpQCT) to measure bone micro-architecture and strength, along with assessment of body composition, glucose metabolism, physical activity and nutrition to better understand the factors that may interfere with adequate bone formation in childhood and adolescence, a critical time for bone growth and lifelong bone health.
