Abnormal Retinal Vascular Reactivity in Individuals with Impaired Glucose Tolerance: A Preliminary Study

Abstract

To investigate the relationship between vascular function parameters measured at the retinal and systemic level and known markers for cardiovascular risk in patients with impaired glucose tolerance (IGT). Sixty age- and sex-matched white European adults (30 with IGT and 30 with normal glucose tolerance [NGT]) were recruited for the study. Fasting plasma glucose, lipids, and 24-hour blood pressure (BP) were measured in all subjects. Systemic vascular and endothelial function was assessed by using carotid-artery intimal media thickness (cIMT) and flow-mediated dilation (FMD). Retinal vascular reactivity was assessed by the dynamic retinal vessel analyzer. Additionally, blood glutathione (reduced glutathione [GSH], glutathione disulfide [GSSG], and total glutathione [tGSH]) and plasma von Willebrand (vWF) factor levels were also measured. Individuals with IGT demonstrated higher BP values (P < 0.001), fasting triglyceride (TG) levels and TG:high-density lipoprotein (HDL) ratios (P < 0.001) than NGT subjects. Furthermore, total:HDL-cholesterol (HDL-C) ratios and Framingham scores were raised (P = 0.010 and P < 0.001, respectively). Blood glutathione levels (GSH, GSSG, and tGSH) were lower (P < 0.001, P = 0.039, and P < 0.001, respectively) while plasma vWF was increased (P = 0.014) in IGT subjects compared to controls. IGT individuals also demonstrated higher IMT in right and left carotid arteries (P = 0.017 and P = 0.005, respectively) alongside larger brachial artery diameter (P = 0.015) and lower FMD percentage (P = 0.026) and glyceryl trinitrate-induced dilation (P = 0.012) than healthy controls. At the retinal arterial level, the IGT subjects showed higher baseline diameter fluctuations (BDFs) (P = 0.026), longer reaction time (RT) (P = 0.032), and reduced baseline-corrected flicker response (bFR) (P = 0.045). In IGT subjects, retinal BDF correlated with total:HDL (P = 0.003) and HDL-C (P = 0.004). Arterial RT also correlated with FMD (P = 0.017) in IGT but not NGT subjects. In IGT individuals there is a relationship between macro- and microvascular function, as well as a direct correlation between the observed retinal microcirculatory changes and established plasma markers for cardiovascular diseases. Multifactorial preventive interventions to decrease vascular risk in these individuals should be considered.