Pulsatile interaction between the macro-vasculature and micro-vasculature: proof-of-concept among patients with type 2 diabetes

Purpose: It is widely thought that excess pulsatile pressure from increased stiffness of large central arteries (macro-vasculature) is transmitted to capillary networks (micro-vasculature) and causes target organ damage. However, this hypothesis has never been tested. We sought to examine the association between macro- and micro-vasculature waveform features in patients with type 2 diabetes (i.e., those with elevated stiffness; T2D) compared with non-diabetic controls. Methods: Among 13 T2D (68 ± 6 years, 39% male) and 15 controls (58 ± 11 years, 40% male) macro-vascular stiffness was determined via aortic pulse wave velocity (aPWV) and macro-vascular waveforms were measured using radial tonometry. Forearm micro-vascular waveforms were measured simultaneously with macro-vascular waveforms via low power laser Doppler fluxmetry. Augmentation index (AIx) was derived on macro- and micro-vascular waveforms. Target organ damage was assessed by estimated glomerular filtration rate (eGFR) and central retinal artery equivalent (CRAE). Results: aPWV was higher among T2D (9.3 ± 2.5 vs 7.5 ± 1.4 m/s, p = 0.046). There was an obvious pulsatile micro-vascular waveform with qualitative features similar to macro-vasculature pressure waveforms. In all subjects, macro- and micro-vasculature AIx were significantly related (r = 0.43, p = 0.005). In T2D alone, micro-vasculature AIx was associated with eGFR (r = − 0.63, p = 0.037), whereas in controls, macro-vasculature AIx and AP were associated with CRAE (r = − 0.58, p = 0.025 and r = − 0.61, p = 0.015). Conclusions: Macro- and micro-vasculature waveform features are related; however, micro-vasculature features are more closely related to markers of target organ damage in T2D. These findings are suggestive of a possible interaction between the macro- and micro-circulation.