Neuro-vascular coupling and heart rate variability in patients with type II diabetes at different stages of diabetic retinopathy

Nikolaus Hommer; Martin Kallab; Andreas Schlatter; Patrick Janku; René M Werkmeister; Kinga Howorka; Doreen Schmidl; Leopold Schmetterer; Gerhard Garhöfer

doi:10.3389/fmed.2022.1025853

Neuro-vascular coupling and heart rate variability in patients with type II diabetes at different stages of diabetic retinopathy

Front Med (Lausanne). 2022 Nov 10:9:1025853. doi: 10.3389/fmed.2022.1025853. eCollection 2022.

Authors

Nikolaus Hommer¹, Martin Kallab¹, Andreas Schlatter^{1

2

3}, Patrick Janku¹, René M Werkmeister⁴, Kinga Howorka⁵, Doreen Schmidl¹, Leopold Schmetterer^{1

4

6

7

8

9}, Gerhard Garhöfer¹

Affiliations

¹ Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
² Hanusch Hospital, Karl Landsteiner Institute, Vienna, Austria.
³ Hanusch Hospital, Vienna Institute for Research in Ocular Surgery, Vienna, Austria.
⁴ Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
⁵ Metabolic Competence Center, Medical University of Vienna, Vienna, Austria.
⁶ Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore.
⁷ Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore.
⁸ School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore.
⁹ Institute of Clinical and Experimental Ophthalmology, Basel, Switzerland.

Abstract

Aims/hypothesis: There is evidence that diabetes is accompanied by a break-down of functional hyperemia, an intrinsic mechanism of neural tissues to adapt blood flow to changing metabolic demands. However, to what extent functional hyperemia is altered in different stages of diabetic retinopathy (DR) in patients with type II diabetes is largely unknown. The current study set out to investigate flicker-induced retinal blood flow changes in patients with type II diabetes at different stages of DR.

Materials and methods: A total of 76 subjects were included in the present parallel-group study, of which 56 had diabetes with either no DR or different stages of non-proliferative DR (n = 29 no DR, 12 mild DR, 15 moderate to severe DR). In addition, 20 healthy subjects were included as controls. Retinal blood flow was assessed before and during visual stimulation using a combined measurement of retinal vessel calibers and blood velocity by the means of Doppler optical coherence tomography (OCT). To measure systemic autonomic nervous system function, heart rate variability (HRV) was assessed using a short-term orthostatic challenge test.

Results: In healthy controls, retinal blood flow increased by 40.4 ± 27.2% during flicker stimulation. Flicker responses in patients with DR were significantly decreased depending on the stage of the disease (no DR 37.7 ± 26.0%, mild DR 26.2 ± 28.2%, moderate to severe DR 22.3 ± 13.9%; p = 0.035, ANOVA). When assessing systemic autonomous neural function using HRV, normalized low frequency (LF) spectral power showed a significantly different response to the orthostatic maneuver in diabetic patients compared to healthy controls (p < 0.001).

Conclusion/interpretation: Our study indicates that flicker induced hyperemia is reduced in patients with DR compared to healthy subjects. Further, this impairment is more pronounced with increasing severity of DR. Further studies are needed to elucidate mechanisms behind the reduced hyperemic response in patients with type II diabetes.

Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT03 552562].

Keywords: diabetes type II; diabetic retinopathy; functional hyperemia; heart rate variability; neuro-vascular coupling; retinal blood flow.

Grants and funding

KLI 721/FWF_/Austrian Science Fund FWF/Austria