title: Alpha adrenoceptor agonist-induced microcirculatory oscillations are reduced in diabetic neuropathy.
abstract: In diabetic patients small fiber neuropathy has been associated with impairment of 0.1 Hz microvascular vasomotion. The aim of this study was (1) to investigate whether vasoconstriction-induced microvascular oscillations in the skin are reduced in diabetic patients with peripheral and/or autonomic neuropathy, and (2) whether this method could be used as a non-invasive surrogate marker to assess diabetic small fiber neuropathy. Four matched groups were studied: diabetic patients without neuropathy (D), with peripheral neuropathy (DPN), with peripheral and autonomic neuropathy (DAN), and non-diabetic controls (Ctrl). All participants were evaluated for peripheral and autonomic neuropathy, microvascular endothelial function, and metabolic syndrome indicators. Laser Doppler flowmetry was used to measure oscillations after iontophoresis of the alpha one selective agonist phenylephrine. approximately 0.1-Hz oscillations recorded at the foot were significantly attenuated in diabetic patients with peripheral and/or autonomic neuropathy (DPN and DAN groups) compared to diabetic patients without neuropathy or non-diabetic controls. In the forearm, microvascular oscillations were significantly reduced only in patients with autonomic neuropathy (DAN). Oscillation measures correlated significantly (P<0.001) with all markers of peripheral neuropathy but not with markers of measurements of microvascular endothelial function, or metabolic syndrome markers. In a logistic regression model, reduced microvascular oscillations at the foot were a strong predictor for the presence of peripheral neuropathy. The measurement of phenylephrine-induced approxiamtely 0.1-Hz microvascular oscillation may represent a useful non-invasive tool with which to study the effects of treatment strategies on the diabetic small fiber neuropathy.
authors.affiliation: Diabetes Centre and Academic Unit, Maelor Hospital, University of Wales College of Medicine, Wrexham LL13, UK. SchmiedelO@cardiff.ac.uk
authors.forename: Ole
authors.initials: O
authors.lastname: Schmiedel
authors.forename: Turo J
authors.initials: TJ
authors.lastname: Nurmikko
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Schroeter
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Whitaker
authors.forename: John N
authors.initials: JN
authors.lastname: Harvey
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000368:Aged; D000419:Albuminuria / Q000652:urine; D001132:Arm / Q000098:blood supply; D016000:Cluster Analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003929:Diabetic Neuropathies / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D005528:Foot / Q000098:blood supply; D005583:Fourier Analysis; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007024:Hypotension, Orthostatic / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D017078:Laser-Doppler Flowmetry; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000503:physiopathology / Q000652:urine; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology*; D008875:Middle Aged; D010656:Phenylephrine / Q000494:pharmacology; D012684:Sensory Thresholds / Q000502:physiology; D012867:Skin / Q000098:blood supply; D014636:Valsalva Maneuver / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D006442:Glycated Hemoglobin; D010656:Phenylephrine; C517652:hemoglobin A1c protein, human