Are metabolic and immune parameters associated with residual beta cell capacity one year after T1D onset?

Background
The course of beta cell function decline is very heterogenous after T1D onset. We aimed to describe the natural course of residual insulin secretion over the first year after T1D diagnosis and to determine the predictors of the partial remission within metabolic and immune parameters.

Methods
A total of 38 children with new onset T1D (20 girls), aged 9.4 years (SD±4) were prospectively followed-up for 1 year. HbA1c and total daily dose of insulin (TDD) were obtained at baseline, 6 and 12 months. The insulin-adjusted A1c (IDAA1c) and partial remission (IDAA1c≤9) were calculated. A mixed-meal tolerance test was performed at 12 months and area under the curve (AUC) of C-peptide was estimated. All subjects were screened for immune markers (Treg,Th17,Th1,MFI BAFFR CD4,MFI BAFFR CD8,CD19,mDC,pDC) at baseline, 6 and 12 months.

Results
A total of 66% of patients achieved partial remission at 6 months as compared to only 45% at month 12. We observed a linear increase of C-peptide AUC with the age of patients (p<0.0001). The TDD of insulin (p<0.009) and IDAA1c (p=0.02) increased significantly with the decrease of C-peptide AUC regardless of age. HbA1c at 12 months was not associated with C-peptide AUC. Dynamics of immune parameters was reflected in an increase of Tregs (p=0.02) and a significant increase of originally low pDCs (p<0.001). Interestingly, the expression of a receptor for BAFF was markedly increased on B lymphocytes (MFI BAFFR CD19; p<0.001) and to a lesser extent also on T lymphocytes over 12 months period regardless of their C-peptide AUC. Curiously, the number of CD4+ BAFFR (p<0.015) and also CD8+ BAFFR expressing cells (p<0.014) were the only ones positively correlated to C-peptide AUC. The correlation between HbA1c and immune parameters varied at all visits.

Conclusion
These data imply that low HbA1c is not associated with partial remission at 12 months. The exact role of changes immune markers for beta cell function decline remains hypothetical.