Glycemic Variability Patterns Strongly Correlate with Partial Remission Status in Children With Newly Diagnosed Type 1 Diabetes

Objective: To evaluate whether indexes of glycemic variability may overcome residual β-cell secretion estimates in the longitudinal evaluation of partial remission in a cohort of pediatric new-onset type 1 diabetes patients.

Research Design and Methods: Values of residual β-cell secretion estimates, clinical parameters (e.g. HbA1C or insulin daily dose) and continuous glucose monitoring (CGM) from 78 new-onset type 1 diabetes pediatric patients were longitudinally collected during one year and cross-sectionally compared. Circadian patterns of CGM metrics were characterized and correlated to remission status using adjusted mixed-effects model. Patients were clustered based on forty-six CGM metrics and clinical parameters, and compared using non-parametric ANOVA.

Results: Study participants had a mean (±SD) age of 10.4 (±3.6) years at diabetes onset and 65% underwent partial remission at +3 months. β-cell residual secretion estimates demonstrated weak-to-moderate correlations with clinical parameters and CGM metrics (r²= 0.05-0.25, p<0.05). However, CGM metrics strongly correlated with clinical parameters (r² >0.52, p<0.05) and were sufficient to distinguish remitters from nonremitters. Also, CGM metrics from remitters displayed specific early morning circadian patterns characterized by increased glycemic stability across days (within 63-140 mg/dL range) and decreased rate of grade II hypoglycemia (p<0.0001), compared to nonremitters. Thorough CGM analysis allowed the identification of four novel glucotypes (p<0.001) that segregate patients into subgroups and mirror the evolution of remission after diabetes onset. 

Conclusion: In our pediatric cohort, combination of CGM metrics and clinical parameters unraveled key clinical milestones of glucose homeostasis and remission status during the first year of type 1 diabetes.