title: Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity.
abstract: Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Forty patients with uncomplicated Type 1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P=0.23). FMD was significantly impaired in patients with Type 1 DM (3.95 compared with 7.75%, P<0.001). Endothelium-independent dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P<0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P=0.001). Wavelet interrogation of postischaemic flow velocity waveforms identified significant differences between groups. In conclusion, 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 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability.
authors.affiliation: Department of Therapeutics and Pharmacology, Whitla Medical Building, Queen's University Belfast, Belfast BT9 7RL, UK. chrislockhart@btinternet.com
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lockhart
authors.forename: Christina E
authors.initials: CE
authors.lastname: Agnew
authors.forename: Aaron
authors.initials: A
authors.lastname: McCann
authors.forename: Paul K
authors.initials: PK
authors.lastname: Hamilton
authors.forename: Cathy E
authors.initials: CE
authors.lastname: Quinn
authors.forename: Damien O
authors.initials: DO
authors.lastname: McCall
authors.forename: Rick D
authors.initials: RD
authors.lastname: Plumb
authors.forename: Vivienne C N
authors.initials: VC
authors.lastname: McClenaghan
authors.forename: R Canice
authors.initials: RC
authors.lastname: McGivern
authors.forename: Mark T
authors.initials: MT
authors.lastname: Harbinson
authors.forename: Gary E
authors.initials: GE
authors.lastname: McVeigh
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000473:pathology; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000473:pathology*; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D033081:Shear Strength; D013314:Stress, Mechanical
chemical_list: D005996:Nitroglycerin