Longitudinal characterization of glycemic trajectories and the role of glyemic variability in childhood type 1 diabetes

Details

Supervisors

Lysy, Philippe

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité spécialisée: sciences biomédicales cliniques

Abstract

enThis thesis aimed to investigate the heterogeneity of glycemic control in children and adolescents with type 1 diabetes (T1D) by combining two complementary approaches: longitudinal HbA1c trajectory analyses and characterization of short-lived hyperglycemic (SLH) episodes using continuous glucose monitoring (CGM) data. The first part of the study focused on the evolution of glycemic control from diagnosis until 18 years of age using data from the IPQE-EAD cohort. Three complementary analytical approaches were applied: latent class growth analysis (LCGA), mean HbA1c classification, and slope-based trajectory classification. Two main glycemic profiles were identified: a stable trajectory and a progressively worsening trajectory. Several factors were associated with poorer glycemic outcomes, including higher BMI, psychosocial stress, ethnic minority status, and severe hypoglycemia. These findings highlight the multifactorial nature of glycemic evolution in pediatric T1D. The second part of the study aimed to characterize SLH episodes using CGM data. A dedicated algorithm identified more than 2,800 SLH episodes in a pediatric cohort. These episodes were frequent but short in duration and were paradoxically associated with more favorable glycemic profiles, including lower HbA1c and higher median glucose. This suggests that SLHs may reflect transient postprandial glucose excursions that are rapidly corrected rather than sustained hyperglycemia. A counterfactual approach was then used to simulate glucose profiles after computational removal of SLH episodes. Although removal of SLHs resulted in only modest improvements in overall glycemic metrics, these episodes may still be clinically relevant because repeated rapid glucose fluctuations could contribute to oxidative stress, glycemic variability, and compensatory behaviors such as “rage bolusing.” Overall, this thesis demonstrates that glycemic control in pediatric T1D cannot be fully captured by HbA1c alone. Integrating longitudinal trajectories with detailed CGM-derived glucose dynamics may improve the understanding of metabolic heterogeneity and support more individualized diabetes management strategies in children and adolescents.