Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes

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/mm2, 95% CI 0.005–0.095) and deep (0.048 pixels/mm2, 95% CI 0.003–0.093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA1c and peak ERG amplitude at 32‐Td·s (r = −0.256, p = 0.028), implicit time at 32‐Td·s (r = 0.422, p