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

Residual β-cell secretion is commonly used as primary endpoint of β-cell mass prevention trials. Recently, peak C-peptide was challenged as a clinically relevant marker of β-cell function considering its poor integration of insulin sensitivity and β-cell glucose responsiveness. In our DIATAG study, we evaluated the correlations between metrics of glycemic variability (GV) and markers of diabetes control (i.e. A1C, insulin daily dose, insulin dose-adjusted A1C [IDAA1C]) to identify whether GV indexes may overcome residual β-cell secretion estimates (BSE) in the evaluation of glucose homeostasis during the first year of type 1 diabetes (e.g. remission period) . Data from 78 new-onset type 1 diabetes pediatric patients were collected from diabetes onset (Δ) and cross-sectionally compared using adjusted mixed-effects models at Δ+3, +12 months for BSE (n=119) and Δ+3, +6, +9, +12 months for glucose control and CGM metrics (n=169) . BSE demonstrated weak-to-moderate correlations with clinical parameters and CGM metrics (r2= 0.05-0.25; p<0.05) . CGM metrics strongly correlated with clinical parameters (r2 >0.52; p<0.05) and were sufficient to distinguish remitters from non-remitters (i.e. IDAA1C respectively <9 or ≥9) . Moreover, CGM metrics from remitters exhibited specific nycthemeral patterns characterized by increased glycemic stability (in 63-160 mg/dL range) across days in the early morning period and decreased grade II hypoglycemia during the day (p<0.01) . Using hierarchical clustering on 46 CGM metrics and clinical parameters (n=169) , we identified four unique glucotypes (p<0.001) during the first year of diabetes that allowed better segregation of intermediate values of IDAA1C from Δ+3 months (38% in Group 1, 26% in Group 2, 29% in Group 3, 7% in Group 4) . We conclude that a 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.