Análise da sensibilidade e especificidade da avaliação da microcirculação através do laser speckle contraste por imagem e dos níveis de biomarcadores de disfunção endotelial com base no Endo-PAT em pacientes com Diabetes tipo 1

Abstract

Endothelial dysfunction (ED) in Type 1 Diabetes (T1D), is a common denominator in the pathophysiology of microvascular and macrovascular complications and is an early marker of cardiovascular risk (CVR). Our aim were to determine the sensitivity and specificity of microcirculation (physiological and pharmacological) assessed through laser speckle contrast imaging (LSCI) and through levels of biomarkers (sVCAM-1 and sICAM-1) based on cutoff values derived from the reactive hyperemia index (RHI) through Endo-PAT, which identifies those with ED in T1D and secondarily to identify clinical, demographic and laboratory parameters associated with impaired endothelial function in these patients. Patients with T1D, aged ≥ 12 years underwent a clinical-epidemiological questionnaire. Were obtained fasting blood samples (lipid profile, glycemic control and levels of C-reactive protein) and at least two samples of urine were collected. Vascular reactivity was assessed in the forearm through the technique of LSCI at baseline, during post occlusive reactive hyperemia (PORH) and during iontophoresis of acetylcholine (ACh) with increasing anodic currents and peripheral arterial tonometry was performed by supplying the RHI through Endo-PAT device. Measurements of sVCAM-1 and sICAM-1 were perfomed though MULTIPLEX assays. 189 patients were evaluated, 97 women (51.3 %) with T1D, aged 32 ± 13 years and with a disease duration of 16 (6-21) years and mean HbA1c of 9.2% (± 2.2) . According to the Receiver Operating Characteristics curve (ROC) analisys, the only test of microvascular reactivity able to identify patients with ED according to RHI ≤ 1.67 was the AUC of ACh (p = 0.002) in those patients with T1D´s duration less than 5 years. The value of 10369 PU presented sensitivity and specificity of 65% and 87,5 %, respectively. No biomarker was able to detect ED through RHI-PAT. On the whole sample, no test of vascular reactivity was able to distinguish the ideal cuttoff based on RHI. The main variables correlated with RHI were age, age at diagnosis, duration of T1D, insulin dose (kg/day), systolic blood pressure (SBP) and capillary glycemia at the day of PAT test, A1c, CRP and glomerular flow rate (GFR). sVCAM-1 levels were correlated to sICAM-1, duration of T1D and capilar glycemia and the levels of sICAM-1 were correlated to AST and ALT. Area under curve (AUC) of PORH was correlated to cardiac frequency at the day of LSCI, AUC of ACh and any significant correlation was found between AUC ACh. In the present study, assessment of microcirculation through endothelium-dependent vasodilation to ACh using LSCI, could distinguish patients with ED according to PAT´s score, presenting sensibilitity and specificity of 65 and 87,5%, respectively, only in those patients with less than 5 years of T1D´s duration with the cuttoff value of 10369 PU, which we suggest to be ideal for this population. No biomarker was able to identify ED according to RHI. The most correlated variables to ED were age, age at diagnosis, duration of DM1, insulin dose (kg/day), systolic blood pressure (SBP) and capillary glycemia at the day of PAT test, A1c, CRP, GFR , AST and ALT.