Multimodal MRI Neurodevelopmental Profiling in Type 1 Diabetes: Long-term Effects of MDI vs CSII Treatments.

Abstract

The developing brain is particularly vulnerable to glycemic extremes in early-onset type 1 diabetes (T1D). However, how treatment-specific modalities may influence long-term neurodevelopmental trajectories remains poorly understood. To characterize multimodal MRI neurodevelopmental profiles in pediatric T1D and evaluate treatment-related effects of Multiple Daily Injections (MDI) versus Continuous Subcutaneous Insulin Infusion (CSII) on brain structure, function, and test whether HbA1c-linked imaging features relate to executive-working-memory performance. Sixteen children with T1D (8 MDI, 8 CSII from diagnosis) and eight controls underwent structural MRI, diffusion MRI, and resting-state fMRI. Union Recursive Feature Elimination (U-RFE) selected gray-matter (GM), white-matter (WM), and functional connectivity (rs-FC) features discriminating groups; regression related selected features to long-term age-adjusted mean glycated hemoglobin (HbA1c). NEPSY-II Word List Interference (WI) was administered; control-referenced WI outcomes were examined versus HbA1c and HbA1c-associated structural features, including mediation. Functional features outperformed structural features (balanced accuracy 0.83 vs 0.67). MDI showed reduced GM/WM integrity and disrupted fronto-temporal and subcortical connectivity versus CSII and controls. Right inferior frontal gyrus (IFG) volume correlated with HbA1c (r=0.71, p<0.05) and predicted HbA1c (β=0.28, p=0.015). Higher HbA1c related to poorer WI repetition (r=-0.60, p=0.013), and right IFG volume related to poorer WI repetition (r=-0.70, p=0.002). Mediation supported an indirect HbA1c effect via right IFG volume (a×b=-0.676; Sobel z=-1.765, one-tailed p=0.0388), explaining ∼64% of the total association. CSII had 30% lower hyperglycemia exposure than MDI and higher WI repetition mean ranks (11.19 vs 5.81; p=0.023). Pediatric T1D is associated with multimodal neuroimaging alterations influenced by insulin treatment modality. CSII may confer neuroprotective benefits by improving metabolic control and preserving functional connectivity. Right IFG volume is a candidate imaging marker linking metabolic regulation to interference-sensitive executive-working-memory vulnerability.