Aims: Recently, our team introduced the concept of post-hypoglycemic hyperglycemia (PHH) in the context that recovery of hypoglycemia impacts cardiovascular risk. GLUREDIA study aimed to evaluate whether PHH parameters correlated with glycemic 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 study, longitudinal values of clinical parameters, continuous glucose monitoring metrics and residual beta-cell secretion from children with new-onset type 1 diabetes were analyzed for one year. PHH is defined as any hypoglycemia followed within two hours by hyperglycemia. PHH parameters were calculated using an in-house built algorithm. Cross-sectional correlations between PHH parameters (i.e., PHH frequency, PHH duration, PHH⊂AUC</SUB>) and glycemic homeostasis markers were performed using adjusted mixed-effects models.
Results: PHH parameters were strong markers to differentiate remitters from non- remitters (all P< 0.001), the most sensitive being PHH/Hyperglycemia duration ratio (cut-off < 0.02, sensibility: 86%, specificity: 68%). Among those, PHH⊂AUC</SUB> correlated with clinical parameters and continuous glucose monitoring metrics and inversely correlated with residual beta-cell secretion (all R2 > 0.22, P< 0.001). Furthermore, combination of PHH parameters identified three groups of patients that might benefit from distinct therapeutic management. Finally, patient classification into four glucotypes, as previously described, independently validated PHH parameters as reliable markers of glycemic homeostasis and improved the segregation of patients with intermediate values of IDAA
Conclusion: PHH parameters are new minimal-invasive and easily assessed markers of partial remission and glycemic homeostasis during the first year of type 1 diabetes that allow patient-specific therapeutic management.