TY - JOUR
T1 - Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes
AU - Kirthi, Varo
AU - Reed, Kate I
AU - Alattar, Komeil
AU - Zuckerman, Benjamin P
AU - Bunce, Catey
AU - Nderitu, Paul
AU - Alam, Uazman
AU - Clarke, Bronagh
AU - Hau, Scott
AU - Al-Shibani, Fatima
AU - Petropoulos, Ioannis N
AU - Malik, Rayaz A
AU - Pissas, Theodoros
AU - Bergeles, Christos
AU - Vas, Prashanth
AU - Hopkins, David
AU - Jackson, Timothy L
N1 - Funding Information:
None of the authors have any relevant financial disclosures to declare. LKC Technologies Inc. and Impeto Medical Inc. provided free use of the RETeval and SUDOSCAN devices, respectively, for this study. PN is funded by Diabetes UK. CaB is part‐funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. The views expressed are those of the author(s) and not necessarily those of Diabetes UK, the NIHR or the Department of Health and Social Care.
Publisher Copyright:
© 2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.
PY - 2022/8/30
Y1 - 2022/8/30
N2 - Aim: To explore if novel non-invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes. Methods: 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). Results: 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
2, 95% CI 0.005–0.095) and deep (0.048 pixels/mm
2, 95% CI 0.003–0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA
1c 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). Conclusions: 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.
AB - Aim: To explore if novel non-invasive diagnostic technologies identify early small nerve fibre and retinal neurovascular pathology in prediabetes. Methods: 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). Results: 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
2, 95% CI 0.005–0.095) and deep (0.048 pixels/mm
2, 95% CI 0.003–0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA
1c 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). Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=85137747942&partnerID=8YFLogxK
U2 - 10.1111/dme.14952
DO - 10.1111/dme.14952
M3 - Article
C2 - 36054221
SN - 0742-3071
SP - e14952
JO - Diabetic medicine : a journal of the British Diabetic Association
JF - Diabetic medicine : a journal of the British Diabetic Association
ER -
