Linear and Nonlinear Directed Connectivity Analysis of the Cardio-Respiratory System in Type 1 Diabetes.

In this study, we explored the possibility of developing non-invasive biomarkers for patients with type 1 diabetes (T1D) by quantifying the directional couplings between the cardiac, vascular, and respiratory systems, treating them as interconnected nodes in a network configuration. Towards this goal, we employed a linear directional connectivity measure, the directed transfer function (DTF), estimated by a linear multivariate autoregressive modelling of ECG, respiratory and skin perfusion signals, and a nonlinear method, the dynamical Bayesian inference (DBI) analysis of bivariate phase interactions. The physiological data were recorded concurrently for a relatively short time period (5 min) from 10 healthy control subjects and 10 T1D patients. We found that, in both control and T1D subjects, breathing had greater influence on the heart and perfusion with respect to the opposite coupling direction and that, by both employed methods of analysis, the causal influence of breathing on the heart was significantly decreased ( < 0.05) in T1D patients compared to the control group. These preliminary results, although obtained from a limited number of subjects, provide a strong indication for the usefulness of a network-based multi-modal analysis for the development of biomarkers of T1D-related complications from short-duration data, as well as their potential in the exploration of the pathophysiological mechanisms that underlie this devastating and very widespread disease.