Impaired coronary and retinal vasomotor function to hyperoxia in Individuals with Type 2 diabetes

Abstract

Purpose: Adults with diabetes are at a high risk of developing coronary heart disease. The purpose of this study was to assess coronary artery vascular function non-invasively in individuals with and without Type 2 diabetes and to compare these coronary responses to another microvascular bed (i.e. retina). We hypothesized that individuals with diabetes would have impaired coronary reactivity and that these impairments would be associated with impairments in retinal reactivity.

Methods: Coronary blood velocity (Transthoracic Doppler Echocardiography) and retinal diameters (Dynamic Vessel Analyzer) were measured continuously during five minutes of breathing 100% oxygen (i.e. hyperoxia) in 15 persons with Type 2 diabetes and 15 age-matched control subjects. Using fundus photographs, retinal vascular calibers were also measured (central retinal arteriole and venule equivalents).

Results: Individuals with diabetes compared to controls had impaired coronary (-2.34±16.64% vs. -14.27±10.58%, P=0.03) and retinal (arteriole: -0.04±3.34% vs. -3.65±5.07%, P=0.03; venule: -1.65±3.68% vs. -5.23±5.47%, P=0.05) vasoconstrictor responses to hyperoxia, and smaller central arteriole-venule equivalent ratios (0.83±0.07 vs. 0.90±0.07, P=0.014). Coronary reactivity was associated with central retinal arteriole equivalents (r=-0.516, P=0.005) and retinal venular reactivity (r=0.387, P=0.034).

Conclusion: Diabetes impairs coronary and retinal microvascular function to hyperoxia. Impaired vasoconstrictor responses may be part of a systemic diabetic vasculopathy, which may contribute to adverse cardiovascular events in individuals with diabetes.

Keywords: Coronary reactivity; Diabetes; Hyperoxia; Retinal reactivity; Vasoconstriction.

Figure 1. Experimental protocol

After baseline measurements (one minute) at room air, hyperoxia stimulus was applied for five minutes and then returned back to room air for three minutes of recovery. Retinal imaging with hyperoxia occurred first and then after 30 minutes of rest, coronary imaging during the hyperoxia was performed.

Figure 2. Coronary and Retinal Imaging

TTDE is a novel non-invasive technique used to measure coronary flow velocity in the distal epicardial coronary artery (A). The Dynamic Vessel Analyzer is able to provide continuous imaging of the retinal blood vessels (B). The retinal arteriole and venule are noted by the circled (A) and (V). Static fundus photographs using special Visualis software calculated a total average equivalent of the all the marked arteriole (red) and venule (blue) calibers (C).

Figure 3. Temporal retinal and coronary responses to hyperoxia

Individuals with diabetes compared to healthy controls had impaired coronary artery vasoconstrictor responses to hyperoxia throughout hyperoxia (one, three, and five minutes) (A). The percent changes in retinal arteriolar diameter responses to hyperoxia were attenuated in individuals with diabetes compared to healthy controls with significant differences observed at five minutes of hyperoxia (B). Similar responses were seen in the retinal venules (C). Type2DM =Type 2 Diabetics; * P<0.05 significant difference between individuals with diabetes compared to healthy controls.

Figure 4. Retinal and coronary reactivity correlations

With all the groups combined, smaller retinal central arteriole equivalents were associated with attenuated coronary vasoconstriction to hyperoxia (A). Attenuated venular reactivity was associated with attenuated coronary reactivity in response to hyperoxia (B). Black circles = controls; Open circles = Type 2 Diabetics.