Multimodal MRI neurodevelopmental profiling in type 1 diabetes: long-term effects of MDI vs CSII treatments

Context 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. Objective To characterize multimodal MRI neurodevelopmental profiles in pediatric T1D and evaluate treatment-related effects of multiple daily injections (MDI) vs continuous subcutaneous insulin infusion (CSII) on brain structure, function, and test whether glycated hemoglobin (HbA1c)-linked imaging features relate to executive-working-memory performance. Methods Sixteen children with T1D (8 MDI and 8 CSII from diagnosis) and eight controls underwent structural MRI, diffusion MRI, and resting-state fMRI. Union Recursive Feature Elimination selected gray matter (GM), white matter (WM), and resting-state functional connectivity (rs-FC) features discriminating groups; regression related selected features to long-term age-adjusted mean HbA1c. NEPSY-II Word List Interference (WI) was administered; control-referenced WI outcomes were examined vs HbA1c and HbA1c-associated structural features, including mediation. Results 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 vs CSII and controls. Right inferior frontal gyrus (IFG) volume correlated with HbA1c (r = 0.71, P < .05) and predicted HbA1c (beta = 0.28, P = .015). Higher HbA1c related to poorer WI repetition (r = -0.60, P = .013), and right IFG volume related to poorer WI repetition (r = -0.70, P = .002). Mediation supported an indirect HbA1c effect via right IFG volume (a & times; b = -0.676; Sobel z = -1.765, one-tailed P = .0388), explaining similar to 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 = .023). Conclusion 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.