Key result
Early-onset T1D and worse glycemic control linked to slower gray and white matter growth versus controls.
Why the study?
The extent to which glycemic exposure adversely impacts the developing brain in young children with early-onset type 1 diabetes is controversial.
Does early-onset type 1 diabetes and cumulative hyperglycemic exposure affect brain growth in young children compared to nondiabetic controls?
Cohort (n=203)
Yes
Does early-onset type 1 diabetes and cumulative hyperglycemic exposure affect brain growth in young children compared to nondiabetic controls?
Early-onset type 1 diabetes and worse glycemic control are associated with slower cortical and subcortical gray and white matter growth in young children.
Persistent brain volume and IQ deficits in early-onset T1D were associated with hyperglycemia; leaves open whether intensified control alters neurodevelopmental trajectories.
Background: The extent to which glycemic exposure adversely impacts the developing brain in young children with early-onset type 1 diabetes (T1D) is controversial. Methods: As part of the multisite DirecNet Study, we performed structural MRI at three time points (baseline, 18 months and approximately 2.9 years after the second visit) in 137 children with T1D (age: 7.0 ± 1.7 years, lifetime average HbA1c: 8.0 ± 0.7%, and diabetes duration: 2.4 years at study entry) and 66 age-matched nondiabetic controls (7.0 1.8 years old). White matter (WM) and gray matter (GM) volumes in various brain regions-of-interest were determined by voxel-based morphometry (VBM). Total cumulative hyperglycemic exposure was determined as HbA1c area under the curve (lifetime A1c) from the time of diagnosis in T1D children. Results: Children with T1D had slower growth of total cortical and subcortical GM and WM than the nondiabetic controls at all timepoints. Gray matter regions (frontal, temporal, subcortical, and occipital cortex) showed less growth in the T1D compared to the control group (p<0.05 family wise error (FWE)-corrected), as did white matter areas (temporal, parietal, and occipital white matter) (p<0.05 FWE-corrected). The occipital-cerebellar and basal ganglia regions appeared to be most vulnerable to the effects of T1D in children. The regions of slower growth were associated with higher lifetime A1c values (p<0.05 false discovery rate (FDR)-corrected). Conclusion: This study demonstrates that children with early-onset T1D and worse glycemic control have slower cortical and subcortical GM and WM growth than nondiabetic controls, suggesting that hyperglycemia is detrimental to the developing brain during this critical period of rapid brain maturation. The long-term consequences of these early alterations in brain growth require further follow-up. Disclosure A. Arbelaez: None. S. O’Donoghue: None. N. Mauras: Consultant; Self; Novo Nordisk Inc., PicoLife. Research Support; Self; Medtronic MiniMed, Inc. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care. N.H. White: None. S.A. Weinzimer: Consultant; Self; Eli Lilly and Company, Sanofi. Consultant; Spouse/Partner; Tandem Diabetes Care. Consultant; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Stock/Shareholder; Self; InsuLine Medical Ltd. T. Aye: None. E. Tsalikian: None. D.M. Wilson: Advisory Panel; Self; Tolerion, Inc. Research Support; Self; Beta Bionics, Dexcom, Inc., Medtronic. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited. M. Tansey: Advisory Panel; Self; Daiichi Sankyo Company, Limited. A. Cato: None. T. Hershey: Research Support; Spouse/Partner; Sage Pharmaceuticals. L.A. Fox: None. K.A. Englert: Consultant; Self; PicoLife Technologies, LLC. A.L. Reiss: None.
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Arbeláez et al. (2019) conducted a cohort in Type 1 Diabetes (n=203). Early-onset type 1 diabetes and hyperglycemic exposure vs. Nondiabetic controls was evaluated on Growth of total cortical and subcortical gray matter (GM) and white matter (WM) (p=<0.05). Early-onset type 1 diabetes and worse glycemic control were associated with slower cortical and subcortical gray and white matter growth compared to nondiabetic controls (p<0.05 FWE-corrected).
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