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

Mélanie Henderson, Matthias Friedrich, Andraea Van Hulst, Catherine Pelletier, Tracie A Barnett, Andrea Benedetti, Jean-Luc Bigras, Vicky Drapeau, Jean-Claude Lavoie, Emile Levy, Marie-Eve Mathieu, Anne-Monique Nuyt, Mélanie Henderson, Matthias Friedrich, Andraea Van Hulst, Catherine Pelletier, Tracie A Barnett, Andrea Benedetti, Jean-Luc Bigras, Vicky Drapeau, Jean-Claude Lavoie, Emile Levy, Marie-Eve Mathieu, Anne-Monique Nuyt

Abstract

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.

Keywords: cardiovascular imaging; coronary heart disease; general diabetes; paediatric cardiology; preventive medicine.

Conflict of interest statement

Competing interests: MH was funded by a Canadian Society for Endocrinology and Metabolism/Astra-Zeneca Diabetes Junior Investigator Award, and is the recipient of the 2019 Canadian Society for Endocrinology and Metabolism Young Investigator Award. MF is board member, shareholder and advisor of Circle Cardiovascular Imaging Inc.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Schematic representation of patient timeline for data collection.

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