Endothelial dysfunction due to decreased nitric oxide bioavailability in dysglycaemic subjects and first-degree relatives of type 2 diabetic patients. (3rd October 2022)

• Record Type: Journal Article
• Authors: Ikonomidis, I; Pavlidis, G; Tsoumani, M; Kousathana, F; Katogiannis, K; Tsilivarakis, D; Thymis, J; Kountouri, A; Korakas, E; Pliouta, L; Parissis, J; Bamias, A; Filippatos, G; Andreadou, I; Lambadiari, V
• Is Part Of: European heart journal. Volume 43(2022)Supplement 2
• Publication Date: 2022-10-03
• Subjects: Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehac544.2413
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Background/Introduction: Oxidative stress plays an important role in the pathogenesis of type 2 diabetes mellitus. Purpose: We aimed to investigate oxidative stress and nitrites/nitrates concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDR) of type 2 diabetic patients with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic). Methods: Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm (Microscan, Glycocheck), a marker of endothelial glycocalyx integrity, coronary flow reserve (CFR) in the distal left anterior descending coronary artery, left ventricular global longitudinal strain (GLS), malondialdehyde (MDA), protein carbonyls (PC) and nitrites/nitrates plasma levels were assessed at 0 and 120 min of a 2-hour OGTT. Insulin sensitivity was evaluated using Matsuda and insulin sensitivity index (ISI). Results: In all subjects, there were no significant changes in MDA and PC at 120 min after OGTT (p>0.05). Compared with normoglycaemic subjects, in FDR and dysglycaemic subjects, nitrites/nitrates levels were significantly decreased at 120 min (−24% versus −30% versus −3%, respectively) with a parallel increase in PBR (+7% versus +10% versus −3%) and a reduction in CFR (−11% versus −14% versus −6%) and GLS (−4% versus −4% versus +0.1%) (p<0.05 for all comparisons). The percent reduction of nitrites/nitrates levels was associated with abnormal values of Matsuda and ISI, reversely related with the percent increase of PBR (r=−0.60, p=0.001) and positively related with the percent decrease of CFR (r=0.39, p=0.038) and GLS (r=0.48, p=0.008). Conclusion: Insulin resistance determines acute endothelial responses during OGTT leading to reduced nitric oxide production with resultant coronary and myocardial dysfunction in FDR and dysglycaemic subjects. Funding Acknowledgement: Type of funding sources: None.