Longitudinal effect of glycaemic variability on retinal neurodegeneration and neuropathic characteristics in paediatric patients with type 1 diabetes mellitus

Retinal neurodegeneration (RN) is an early marker of diabetic retinopathy, preceding vascular damage. The aims of our study are to evaluate the three-year progression of neuroretinal structure, the association between early alterations and diabetic neuropathy (DN) and the predictive role of glycaemic variability (GV) in this progression in paediatric type 1 diabetes mellitus (T1DM) subjects. Twenty-five paediatric T1DM patients, using Continuous Glucose Monitoring (CGM) and treated with continuous subcutaneous insulin infusion, without any complication, and eighteen controls (C) were enrolled and followed for three years. All subjects underwent an Optical Coherence Tomography, with analysis of neuroretinal layers. In T1DM patients, metabolic parameters, GV indexes, standardised CGM metric, peripheral and autonomic assessment were investigated. All the data were collected at baseline and every 12 months. Starting from the baseline, Retinal Nerve Fiber Layer thickness and Outer Plexiform Layer (OPL) became significantly thinner in T1DM versus C. In T1DM patients, negative correlations were observed between GV and all the inner retinal layers and positive correlations were observed between TIR and OPL. No significant correlations between HbA1c and macular layer thickness were observed. At V3, positive correlations between the retinal variation and neuropathic indexes were observed. Early morphological alterations of neuroretina are already present in paediatric T1DM patients without complications. There is a possible association between these alterations and early signs of DN. These data corroborate the hypothesis that RN is an early sign of DN and GV should be effectively addressed in the early stage of T1DM.