1518-P: Worsening of Microvascular Reactivity and Markers of Endothelial Activation and Oxidative Stress in Patients with Stabilized Type 1 Diabetes: 3-Year Follow-Up

Abstract

Endothelial activation accelerated by oxidative stress (OxS) is believed to be the major step in development of diabetes angiopathy. The aim of this follow-up study was to measure microvascular reactivity (MVR) and markers of OxS. Our study involved 87 patients with type 1 diabetes (aged 37 ± 15 yrs, HbA1C 7.8 ± 1.5 % DCCT, DM duration 18 ± 11 yrs). MVR was evaluated from post-occlusive reactive hyperemia (PORH) by Laser-Doppler fluxmetry (Perimed) and skin autofluorescence (SAF), reflecting advanced glycation endproducts (AGEs) accumulation, was assessed by AGE-Reader (Diagnoptics). OxS was evaluated by malondialdehyde (MDA), derivatives of reactive oxygen metabolites (d-ROMs) test and plasma antioxidant test (PAT) (FRAS4). Markers of endothelial activation (ICAM-1, VCAM-1, vWF) and routine biochemical and biometrical parameters were evaluated in all patients during 3 years of follow-up. Diabetes control slightly improved during the study period (HbA1c 7.8 ± 1.5 vs. 7.5 ± 1.4 % DCCT, p<0.05), while SAF remained almost unchanged (2.1 ± 0.5 vs. 2.3 ± 0.5 AU, ns). Worsening of MVR was observed (Time to max PORH 12.7 vs. 17.5 s, p<0.05). Significant increase in VCAM-1 was present (718 ± 186 vs. 918 ± 550 pg/L, p<0.005), while ICAM-1 and vWF did not change significantly. Both higher MDA (0.70 ± 0.26 vs. 0.81 ± 0.23 µmol/L, p<0.05) and PAT (2431 ± 645 vs. 2944 ± 466 U Cor, p<0.0001) were observed. Skin autofluorescence was positively associated with vibration perception threshold (r=0.45, p<0.0001) and HbA1c (r=0.24, p<0.005). Although diabetes control slightly improved, we observed further progression of endothelial dysfunction and oxidative stress in our T1D patients. Higher AGEs accumulation in patients with worse glucose control was associated with impaired vibration perception threshold. It is questionable whether boosted human antioxidant capacity in subject with increased OxS could be considered protective and beneficial. Disclosure J. Skrha: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. J. Soupal: Advisory Panel; Self; Abbott. Consultant; Self; Medtronic, Roche Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc. M. Prazny: Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Roche Diabetes Care. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. Funding RVO VFN64165, Progres Q25