Multimodal testing reveals subclinical neurovascular dysfunction in prediabetes, challenging the diagnostic threshold of diabetes. Issue 3 (12th September 2022)

• Record Type: Journal Article
• Authors: Kirthi, Varo; Reed, Kate I.; Alattar, Komeil; Zuckerman, Benjamin P.; Bunce, Catey; Nderitu, Paul; Alam, Uazman; Clarke, Bronagh; Hau, Scott; Al‐Shibani, Fatima; Petropoulos, Ioannis N.; Malik, Rayaz A.; Pissas, Theodoros; Bergeles, Christos; Vas, Prashanth; Hopkins, David; Jackson, Timothy L.
• Is Part Of: Diabetic medicine. Volume 40:Issue 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-12
• Subjects: neuropathy‐somatic -- prediabetes -- retinopathy; Diabetes -- Periodicals; 616.462
• DOI: 10.1111/dme.14952
• Languages: English
• ISSNs: 0742-3071

Abstract

Abstract: 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 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 < 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.