Impaired Flow Mediated Dilatation response in Uncomplicated Type 1 Diabetes Mellitus: influence of shear stress and microvascular reactivity

Christopher J Lockhart (1) , Christina E Agnew , Aaron Mccann , Paul K Hamilton , Cathy E Quinn , Damien O Mccall , Rick D Plumb , Vivienne Mcclenaghan , Canice R Mcgivern , Mark T Harbinson , Gary Mcveigh

1 Department of Therapeutics and Pharmacology

Objective Impaired flow-mediated dilatation (FMD) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as diabetes mellitus (DM). Endothelium-dependent FMD is a homeostatic response to short-term increases in local shear stress. Microvascular dysfunction in diabetes mellitus influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked diastolic shear stress (DSS) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Methods and Results 40 patients with uncomplicated type 1 diabetes and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Post ischaemic Doppler velocity spectral envelopes were recorded, and a wavelet-based time-frequency spectral analysis method employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 vs. 3.94, p=0.23). FMD (%) was significantly impaired in patients with type 1 diabetes (3.95 vs. 7.75, p<0.001). Endothelium-independent dilatation (%) in response to glyceryl trinitrate (GTN) was also significantly impaired (12.07 vs. 18.77, p<0.001). DSS (dyne/cm²) was significantly reduced in the patient group (mean 20.19 vs. 29.5, p=0.001). Wavelet interrogation of post-ischaemic flow velocity waveforms identified significant differences between groups. Conclusions DSS, microcirculatory function and endothelium-independent vasodilatation in response to GTN, are important determinants that impact on the magnitude of FMD response, and are impaired in patients with type 1 diabetes mellitus. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished Nitric Oxide (NO) bioavailability. Clinical trials no: NCT01045005

Mots clés: Medicine

Domaines: Médecine humaine et pathologie

Christopher J Lockhart, Christina E Agnew, Aaron Mccann, Paul K Hamilton, Cathy E Quinn, et al.. Impaired Flow Mediated Dilatation response in Uncomplicated Type 1 Diabetes Mellitus: influence of shear stress and microvascular reactivity. Clinical Science, 2011, 121 (3), pp.129-139. ⟨10.1042/CS20100448⟩. ⟨hal-00687791⟩