Η επίδραση της οξείας υπερομοκυστεϊναιμίας στη μικροκυκλοφορία του δέρματος σε ασθενείς με σακχαρώδη διαβήτη τύπου 2: μία μελέτη με τη χρήση της ιοντοφόρησης

Abstract

The aim of this study was to investigate the effects of acute, methionineinducedhyperhomocysteinaemia on endothelial function of the skinmicrocirculation in diabetic compared with non-diabetic persons. Endothelialandnon-endothelial- dependent vasodilatation of the skin microcirculationwere evaluated in 20 persons with type 2 diabetes (59.95±2.36 years old) and24 age- and gender-matched controlsEndothelial function of the skin microcirculation was assessed using thelaser Doppler technique, combined with iontophoresis of vasoactivesubstances acetylcholine [Ach] and sodium nitroprusside [SNP] through theskin, both at baseline (fasting state) and 4 h after methionine load. Ach, anendothelium-dependent vasodilator, acts via release of nitric oxide (NO) fromthe endothelium, whereas SNP causes endothelial-independent vasodilatation,acting directly on the smooth muscle cells, as a direct NO donor.A laser Doppler instrument and a micropharmacology system were usedfor non-invasive and continuous measurement of perfusion changes duringvascular provocations in the skin. The drug delivery electrode was filled with140 l Ach 1% or SNP 1% and was attached with the laser probe to the volarsurface of the right forearm. Ach (1%) was delivered using an anodal current:7x0.1 mA (milliapere) for 20 s,followed by 1x0.2 mA for 20 s, with a 60-sinterval between each dose to produce a cumulative dose-response curve(total charge 18 millicoulombs – mC). Forearm skin erythrocyte flux wasrecorded immediately before the start of iontophoresis and after each periodof drug application. Using a new delivery electrode, 1% of SNP was deliveredusing a cathodal current: 2x0.1 mA for 20 s, followed by 1x 0.2 mA for 20 swith 180-s interval between each dose ( total charge 8 mC).When examining the effects of the vasoactive substances on the skinmicrocirculation between the two groups (diabetic patients and controls ), itwas noted that in the fasting state, iontophoretically applied Ach caused asimilar vasodilator response in both diabetic patients and control subjects (p =0,174), whereas, after methionine-induced HHcy 4h later, Ach applicationcaused a significantly more blunted vasodilator response in the diabetic patients compared with the controls. ([mean±SEM] 8.09±1.18-fold increase indiabetic patients vs. 11.11±1.33-fold increase in controls, p=0.027). Similarly,iontophortically applied SNP in the fasting state caused an analogousvasodilator response both in diabetic patients and in control subjects (p=0,642), whereas after methionine-induced HHcy 4h later, SNP applicationcaused a significantly more reduced vasodilator response in the diabeticpatients compared with the controls. ([mean±SEM] 7.55±0.80-fold increase inthe diabetic patients vs. 12.19±1.26- fold increase in controls, p=0.008).This study suggests that acute, methionine – induced hyperhomocysteinaemiacauses more reduced microvascular vasodilator effects (bothendothelial- and non-endothelial-dependent ) in T2DM patients compared withnon-diabetic controls. Previous studies have examined the influence of HHcy,both chronic, as well as acute, methionine-induced, on endothelial function inhealthy persons. The literature concerning the effects of HHcy on endothelialfunction in diabetic patients is scarce though, and restricted only to theinfluence of chronic HHcy on the macrovasculature. These functionalalterations may contribute to the observed heightened cardiovascular riskseen in T2DM patients with HHcy as well as to the increased microvascularrisk seen in type 2 diabetes patients with high Hcy levels.