Kirthi, Varo, Reed, Kate I, Alattar, Komeil, Zuckerman, Benjamin P, Bunce, Catey, Nderitu, Paul, Alam, Uazman 
ORCID: 0000-0002-3190-1122, Clarke, Bronagh, Hau, Scott, Al-Shibani, Fatima et al (show 7 more authors)
(2023)
Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes.
DIABETIC MEDICINE, 40 (3).
e14952-.
Abstract
<h4>Aim</h4>To explore if novel non-invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes.<h4>Methods</h4>Participants with normoglycaemia, prediabetes or type 2 diabetes underwent an exploratory cross-sectional analysis with optical coherence tomography angiography (OCT-A), handheld electroretinography (ERG), corneal confocal microscopy (CCM) and evaluation of electrochemical skin conductance (ESC).<h4>Results</h4>Seventy-five participants with normoglycaemia (n = 20), prediabetes (n = 29) and type 2 diabetes (n = 26) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16-Td·s: 4.05 μV, 95% confidence interval [95% CI] 0.96-7.13) and high (32-Td·s: 5·20 μV, 95% CI 1.54-8.86) retinal illuminance were lower in prediabetes, as were OCT-A parafoveal vessel densities in superficial (0.051 pixels/mm<sup>2</sup> , 95% CI 0.005-0.095) and deep (0.048 pixels/mm<sup>2</sup> , 95% CI 0.003-0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA<sub>1c</sub> and peak ERG amplitude at 32-Td·s (r = -0.256, p = 0.028), implicit time at 32-Td·s (r = 0.422, p < 0.001) and 16-Td·s (r = 0.327, p = 0.005), OCT parafoveal vessel density in the superficial (r = -0.238, p = 0.049) and deep (r = -0.3, p = 0.017) retinal layers, corneal nerve fibre length (CNFL) (r = -0.293, p = 0.017), and ESC-hands (r = -0.244, p = 0.035) were observed. HOMA-IR was a predictor of CNFD (β = -0.94, 95% CI -1.66 to -0.21, p = 0.012) and CNBD (β = -5.02, 95% CI -10.01 to -0.05, p = 0.048).<h4>Conclusions</h4>The glucose threshold for the diagnosis of diabetes is based on emergent retinopathy on fundus examination. We show that both abnormal retinal neurovascular structure (OCT-A) and function (ERG) may precede retinopathy in prediabetes, which require confirmation in larger, adequately powered studies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | neuropathy-somatic, prediabetes, retinopathy |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 24 Jan 2023 09:29 |
| Last Modified: | 22 Mar 2023 10:38 |
| DOI: | 10.1111/dme.14952 |
| Open Access URL: | https://doi.org/10.1111/dme.14952 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3167843 |
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