Advanced phenotyping of cardiovascular risk in children with chronic disease- Children with type 1 diabetes and kidney transplant recipients

Abstract

Abstract This thesis aim to determine the presence of early vascular changes in two paediatric cohorts with chronic disease and highly elevated cardiovascular risk, children with kidney transplants (Paper I) and children with type 1 diabetes (Papers II-IV). With sensitive assessment of vascular morphology- and function, as well as cardiac autonomic regulation in the type 1 diabetes cohort, we identified signs of early vascular remodelling reflecting impact on both the intimal- and medial layers of the arterial wall in both study cohorts, as well as signs of subclinical cardiac dysregulation in children with type 1 diabetes. Associated disease specific and/or metabolic variables were also detected, especially in the type 1 diabetes group where both morphological- and functional- vascular variables as well cardiac autonomic regulation showed connections with type 1 diabetes duration, HbA1c and continuous glucose monitoring (CGM) metrics. In papers I and II, ultra-high frequency ultrasound was used to scan the radial, dorsal pedal and carotid arteries and both children with kidney transplants and children with type 1 diabetes had impact on vascular wall thickness compared to age- and sex matched healthy controls. In paper III cardiac autonomic regulation was assessed in children with type 1 diabetes and there was an increased presence of cardiac autonomic dysregulation in those with both type 1 diabetes and overweight. In paper IV ambulatory blood pressure (ABP) measurements were performed at baseline and 2- year follow-up with a decrease across all ABP- variables over two years of follow-up, associated with increased time in normoglycemia. To summarize, the identified signs of early morphological- and functional vascular changes in both study groups indicate a need for further optimization of both traditional- and disease specific cardiovascular risk-factors. Our methods are applicable in various kinds of paediatric chronic conditions and may be considered to further improve cardiovascular risk-factor monitoring in clinical settings.