Relationships between Continuous Glucose Monitoring-Derived Glycemic Parameters and Early Retinal Vascular Changes in Children with Type 1 Diabetes Mellitus

Objective: This study investigated relationships between continuous glucose monitoring (CGM)-derived metrics and early retinal vascular changes in children having type-1 diabetes mellitus (T1DM) with no clinically-visible diabetic retinopathy (T1DM-noR).Methods: Forty-two T1DM-noR patients and 45 healthy children were enrolled.Optical coherence tomography angiography (OCTA) parameters of superficial and deep capillary plexuses (SCP/DCP) were compared between groups.In T1DM-noR group, correlations of OCTA parameters with HbA1c, diabetes duration, time-in-range (TIR), time-in-tight-range (TITR), time-above-range (TAR), glucose-management-indicator (GMI) and coefficient of variation (CV) were examined, followed by adjusted multivariable regressions.Results: Compared to controls, T1DM-noR group showed significantly reduced SCP and DCP vessel densities in whole retina (p=0.038;p=0.017), fovea (p=0.046;p=0.041), parafovea (p=0.025;p=0.012) and perifovea (p=0.032;p=0.021).In T1DM-noR cases, whole retina, fovea, parafovea and perifovea measurements of SCP and DCP were significantly negatively correlated with HbA1c, diabetes duration, TAR, GMI and CV, but positively correlated with TIR and TITR (p<0.05).In multivariable regression, all significant associations in DCP and almost all in SCP remained independent after adjusting for age and diabetes duration (p<0.05).Conclusion: We found that T1DM children had reduced SCP and DCP vessel densities before development of clinically-visible retinopathy.In our study, as TIR and TITR decreased and HbA1c, diabetes duration, TAR, GMI and CV increased, SCP and DCP vessel densities decreased.Our study suggested that reduced densities, independently associated with CGM metrics (especially in DCP), might serve as early indicator of retinal changes in T1DM-noR children, and in such patients, more effective glycemic control should be considered. What is already known on this topic?Previous studies showed that children having type-1 diabetes mellitus with no clinically-visible diabetic retinopathy (T1DM-noR) might exhibit some retinal microvascular changes.Until our study, relationships of retinal vessel densities with time-in-range (TIR), time-in-tight-range (TITR), time-above-range (TAR), glucose management indicator (GMI) and coefficient of variation (CV) had not been comprehensively researched.What this study adds?T1DM children had reduced superficial and deep capillary plexuses (SCP/DCP) vessel densities before clinically-visible retinopathy.As TIR and TITR decreased and HbA1c, diabetes duration, TAR, GMI and CV increased, vessel densities decreased.Reduced densities were independently associated with these metrics after adjusting for age and diabetes duration, especially in DCP.