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Published on: January 4, 2018
Multimodal MRI neurodevelopmental profiling in type 1 diabetes: long-term effects of MDI vs CSII treatments
Pasquale Anthony Della Rosa1,2, Nicolò Pecco1, Sonia Francesca Calloni1
1Department of Neuroradiology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan 20132, Italy.
Insights
Children with type 1 diabetes (T1D) show brain differences, with Continuous Subcutaneous Insulin Infusion (CSII) potentially offering neuroprotection over Multiple Daily Injections (MDI). Right inferior frontal gyrus volume links metabolic control to cognitive function.
Area of Science:
- Neuroscience
- Pediatric Endocrinology
- Medical Imaging
Background:
- The developing brain is highly susceptible to blood sugar fluctuations in early-onset type 1 diabetes (T1D).
- Long-term neurodevelopmental effects of different T1D treatment methods are not well understood.
Purpose of the Study:
- To analyze brain development using MRI in children with T1D.
- To compare the effects of Multiple Daily Injections (MDI) versus Continuous Subcutaneous Insulin Infusion (CSII) on brain structure and function.
- To investigate the relationship between HbA1c levels, brain imaging findings, and executive-working memory performance.
Main Methods:
- Multimodal MRI (structural, diffusion, resting-state fMRI) was used in 16 children with T1D (8 MDI, 8 CSII) and 8 controls.
- Machine learning (U-RFE) identified key brain features (gray matter, white matter, functional connectivity) differentiating groups.
- Regression analyses linked these features to HbA1c, and cognitive tests (NEPSY-II Word List Interference) assessed executive-working memory.
Main Results:
- Functional MRI features were more effective than structural features in distinguishing groups (balanced accuracy 0.83 vs 0.67).
- MDI treatment was associated with reduced gray/white matter integrity and altered brain connectivity compared to CSII and controls.
- Right inferior frontal gyrus volume correlated with HbA1c and predicted poorer executive-working memory, mediating the effect of HbA1c on cognition. CSII group showed better metabolic control and cognitive performance.
Conclusions:
- Pediatric T1D is linked to brain alterations that vary by insulin treatment type.
- Continuous Subcutaneous Insulin Infusion (CSII) may offer neuroprotective advantages through improved metabolic control and preserved brain connectivity.
- The right inferior frontal gyrus volume serves as a potential imaging biomarker connecting metabolic health to executive-working memory deficits in T1D.
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.
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