Cardiovascular disease in young People with Type 1 Diabetes: Search for Cardiovascular Biomarkers

Abstract

Premature onset of cardiovascular disease is common in people with type 1 diabetes and is relatively understudied in youth. Several reports in adolescents and young adults with diabetes demonstrate evidence of arterial stiffness and cardiac dysfunction, yet critical gaps exist in our current understanding of the temporal progression of cardiac and vascular dysfunction in these youth, and mechanistic investigations with robust pathophysiologic assessment are lacking. This review attempts to summarize relevant cardiovascular studies concerning children, adolescents, and young adults with type 1 diabetes. We focus on imaging-based biomarkers routinely applied to youth and adults that are well-established in their ability to predict adjudicated cardiovascular outcomes, and their relevant physiologic interpretation. Particularly, we focus the attention to 1) cardiac ventricular strain imaging techniques which are known to be predictive of clinical outcomes in patients with heterogenous causes of heart failure, and 2) stiffness in large arteries, a well-established prognostic marker of cardiovascular events. We conclude that there remains an urgent need for sensitive and quantitative biomarkers to define the natural history of cardiac and vascular disease origination and progression in type 1 diabetes, and set the stage for interpreting interventional studies focused on preventing, reversing or slowing disease progression.

Keywords: Arterial stiffness; Cardiomyopathy; Pediatric; Type 1 diabetes.

Fig. 1.

Graphical representation of standard echocardiographic measurements of diastolic dysfunction. The blue tracing line interrogates using standard Pulse Wave Doppler technique trans-mistral flow. Prominent E and A wave velocities are reflective of early diastolic inflow and atrial contraction, respectively. Tissue Doppler velocities can be sampled along the septal (purple) or lateral (green) mitral valve annulus. Similarly to trans-mitral Doppler velocities, e′ and a′ waves represent the mitral valve annulus motion during mitral valve opening in early diastole and during atrial contraction, respectively. Pulmonary venous Doppler (black) samples the blood flow velocity in the pulmonary veins. S₁ and S₂ waves occur in systole and represent blood flow acceleration due to atrial relaxation and atrial stretch toward the apex during systole, respectively. D waves represent the blood flow acceleration during the ventricular filling when mitral valve is open.

Fig. 2.

Comparative analysis of representative type 1 diabetes (T1D) patient (A) and control subject (B) strain curves. Resulting systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF) calculations showing are depicted for respective T1D (C) and control (D) subjects. Mean strain rate (dε(t)/dt) represents average positive (red)/negative (black) strain rate at each individual time point. Note that color-highlighted positive and negative strain rate curves represent global average, which is not considered for actual evaluation but only for graphic representation. One can notice relatively higher proportion of the red area (myocardial stretch – relaxation) to the black area (myocardial contraction) during systole in the patient with T1D. Inversely, during diastole there is a higher proportion of the myocardial contraction (black) with respect to thee myocardial relaxation (red) in patient with the T1D. These findings suggest that myocardial regions are not well electromechanically synchronized in patients with T1D.

Fig. 3.

Myocardial deformation or strain analysis can be retrospectively achieved by subjecting either echocardiographic or MRI short and long images to speckle or feature/tissue tracking analyses, respectively. Three deformation components including the circumferential, radial, and longitudinal strain should be reported in order to understand global myocardial function.

Fig. 4.

A) Pulse wave velocity (PWV) assessment using standard phase-contrast MRI. Thoracic aorta is interrogated by using the phase-contrast MRI derived flow curve at variable planes of interest (green, blue, red). Sagittal oblique view of the aorta is also open in order to map the true anatomic intraluminal distance between the planes of interest. B) Generated flow curves from each plane of interest serve for determination peak-to-peak time differences for each aortic segment. PWV is calculated as the ratio of distance over change in time using the respective values. C) Plane – location specific PWV can be further analyzed using the flow-area method directly at the plane of interest.