CARDEA study protocol: investigating early markers of cardiovascular disease and their association with lifestyle habits, inflammation and oxidative stress in adolescence using a cross-sectional comparison of adolescents with type 1 diabetes and healthy controls

INTRODUCTION: Little is known regarding associations between potentially modifiable lifestyle habits and early markers of cardiovascular disease (CVD) in pediatric type 1 diabetes (T1D), hindering early prevention efforts. Specific objectives are: (1) compare established risk factors (dyslipidemia, hypertension) with novel early markers for CVD (cardiac phenotype, aortic distensibility, endothelial function) in adolescents with T1D and healthy age-matched and sex-matched controls; (2) examine associations between these novel early markers with: (i) lifestyle habits; (ii) adipokines and measures of inflammation; and (iii) markers of oxidative stress among adolescents with T1D and controls, and determine group differences in these associations; (3) explore, across both groups, associations between CVD markers and residential neighbourhood features. METHODS AND ANALYSES: Using a cross-sectional design, we will compare 100 participants aged 14–18 years with T1D to 100 healthy controls. Measures include: anthropometrics; stage of sexual maturity (Tanner stages); physical activity (7-day accelerometry); sleep and sedentary behaviour (self-report and accelerometry); fitness (peak oxygen consumption); and dietary intake (three non-consecutive 24- hour dietary recalls). Repeated measures of blood pressure will be obtained. Lipid profiles will be determined after a 12- hour fast. Cardiac structure/function: non-contrast cardiac magnetic resonance imaging (CMR) images will evaluate volume, mass, systolic and diastolic function and myocardial fibrosis. Aortic distensibility will be determined by pulse wave velocity with elasticity and resistance studies at the central aorta. Endothelial function will be determined by flow-mediated dilation. Inflammatory markers include plasma leptin, adiponectin, tumour necrosis factor alpha (TNF-α), type I and type II TNF-α soluble receptors and interleukin-6 concentrations. Measures of endogenous antioxidants include manganese superoxide dismutase, glutathione peroxidase and glutathione in blood. Neighbourhood features include built and social environment indicators and air quality. ETHICS AND DISSEMINATION: This study was approved by the Sainte-Justine Hospital Research Ethics Board. Written informed assent and consent will be obtained from participants and their parents. TRIAL REGISTRATION NUMBER: NCT04304729.