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 (β = 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 × b = -0.676; Sobel z = -1.765, one-tailed P = .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 = .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.