First-degree relatives of type-2 diabetic patients and dysglycaemic patients have impaired endothelial function due to decreased bioavailability of nitric oxide

Abstract

Abstract Background/Introduction Oxidative stress plays an important role in the pathogenesis of type 2 diabetes. Purpose We investigated oxidative stress in first-degree relatives of type-2 diabetes patients (FDR) since they are more prone to develop type-2 diabetes, at baseline and during postprandial hyperglycemia in comparison with dysglycaemic or normoglycaemic subjects. We evaluated these results in relation to vascular function. Methods We studied 40 FDR with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic) with similar demographical and clinical characteristics. Glucose and insulin levels, pulse wave velocity (PWV-Complior, ALAM), central systolic blood pressure (cSBP) and augmentation index (AI) were measured at baseline, 30, 60, 90 and 120min during OGTT. Perfused boundary region (PBR-Microscan, Glycocheck) of the sublingual arterial microvessels (high PBR values represent reduced glycocalyx thickness), plasma concentrations of malondialdehyde (MDA) and protein carbonyls (PCs) as markers of lipid peroxidation and protein oxidation, respectively, and nitrite/nitrates levels as markers for NO biosynthesis, were assessed at baseline and at 120min of OGTT. Insulin sensitivity was evaluated using Matsuda and insulin sensitivity index (ISI). Results FDR and dysglycaemics patients had higher fasting insulin, reduced ISI, Matsuda index as well as increased PBR (2.5±0.5 vs. 2.5±0.6 vs. 2.4±0.3μm), increased PWV (8.9±1.1 vs. 10.3±2.4 vs. 8.0±1.5m/s), AI, MDA, PCs and nitrite/nitrate than normoglycaemic subjects (p<0.05 for all comparisons). ISI was negatively related with PBR and MDA (r=−0.35 and r=−0.34, p<0.05) at baseline in FDR and dysglycaemics. During OGTT, AI was similarly reduced in both normoglycaemics and FDR whereas AI was significantly increased in dysglycaemics at 120min (p<0.05). PBR was increased by 7.5% and 4% at 120min in dysglycaemics and FDR, respectively, while remained unchanged in normoglycaemics (p<0.05). In dysglycaemics and FDR, nitrite/nitrate levels were significantly decreased at 120min (52.85±8.22 vs. 36.31±4.36 and 48.23±7.20 vs. 34.70±4.71nmol/ml, respectively, p<0.05) while they were remained unchanged in normoglycaemics likely leading to a greater decrease of MDA (−83% vs. −40% vs. −48%) and of PCs (−28% vs. −7% vs. −16%) in normoglycaemics compared with dysglycaemics and FDR (p<0.05). Conclusions Insulin resistance determines acute endothelial responses during postprandial hyperglycemia leading to reduced NO production and thus facilitating augmentation of oxidative stress during postprandial hyperglycemia in dysglycaemic patients and FDR of diabetic patients. Funding Acknowledgement Type of funding sources: None.