Post-Hypoglycemic hyperglycemia are highly relevant markers for stratification of glycemic variability and partial remission status of pediatric patients with new-onset type 1 diabetes

AIMS: To evaluate whether parameters of post-hypoglycemic hyperglycemia (PHH) correlated with glucose homeostasis during the first year after type 1 diabetes onset and helped to distinguish pediatric patients undergoing partial remission or not. METHODS: In the GLUREDIA (GLUcagon Response to hypoglycemia in children and adolescents with new-onset type 1 DIAbetes) study, longitudinal values of clinical parameters, continuous glucose monitoring metrics and residual β-cell secretion from children with new-onset type 1 diabetes were analyzed during the first year after disease onset. PHH parameters were calculated using an in-house algorithm. Correlations between PHH parameters (i.e., PHH frequency, PHH duration, PHH area under the curve [PHH(AUC)]) and glycemic homeostasis markers were studied using adjusted mixed-effects models. RESULTS: PHH parameters were strong markers to differentiate remitters from non-remitters with PHH/Hyperglycemia duration ratio being the most sensitive (ratio<0.02; sensitivity = 86% and specificity = 68%). PHH(AUC) moderately correlated with parameters of glucose homeostasis including TIR (R(2) = 0.35, p-value < 0.05), coefficient of variation (R(2) = 0.22, p-value < 0.05) and Insulin-Dose Adjusted A1c (IDAA(1C)) (R(2) = 0.32, p-value < 0.05) and with residual β-cell secretion (R(2) = 0.17, p-value < 0.05). Classification of patients into four previously described glucotypes independently validated PHH parameters as reliable markers of glucose homeostasis and improved the segregation of patients with intermediate values of IDAA(1C) and estimated C-peptide (CPEP(EST)). Finally, a combination of PHH parameters identified groups of patients with specific patterns of hypoglycemia. CONCLUSION: PHH parameters are new minimal-invasive markers to discriminate remitters from non-remitters and evaluate glycemic homeostasis during the first year of type 1 diabetes. PHH parameters may also allow patient-targeted therapeutic management of hypoglycemic episodes.