Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia

Nelly Mauras, Paul Mazaika, Bruce Buckingham, Stuart Weinzimer, Neil H White, Eva Tsalikian, Tamara Hershey, Allison Cato, Peiyao Cheng, Craig Kollman, Roy W Beck, Katrina Ruedy, Tandy Aye, Larry Fox, Ana Maria Arbelaez, Darrell Wilson, Michael Tansey, William Tamborlane, Daniel Peng, Matthew Marzelli, Karen K Winer, Allan L Reiss, Diabetes Research in Children Network (DirecNet), Eva Tsalikian, Michael J Tansey, Julie Coffey, Joanne Cabbage, Sara Salamati, Amy Conrad, Nelly Mauras, Larry A Fox, Ellison Cato, Kim Englert, Kaitlin Sikes, Tina Ewen, Bruce A Buckingham, Darrell M Wilson, Tandy Aye, Kimberly Caswell, Kristin Schleifer, Christian Ambler, Stuart A Weinzimer, William V Tamborlane, Amy Steffen, Kate Weyman, Melinda Zgorski, Jodie Ambrosino, Neil H White, Ana Maria Arbelaez, Lucy Levandoski, Angie Stames, Tamara Hershey, Sarah June Grafeman, Roy W Beck, Katrina J Ruedy, Craig Kollman, Peiyao Cheng, Beth Stevens, Kelly Njeru, Ryan Chapman, Thomas Mouse, Allan L Reiss, Naama Barnea-Goraly, Matthew J Marzelli, Paul M Mazaika, Daniel X Peng, Tamara Hershey, Allison Cato, Emily Bihun, Amal Al-Lozi, Allison Bischoff, Michaela Cuneo, Aiden Bondurant, Mark Sperling, Dorothy M Becker, Patricia Cleary, Carla Greenbaum, Antoinette Moran, Nelly Mauras, Paul Mazaika, Bruce Buckingham, Stuart Weinzimer, Neil H White, Eva Tsalikian, Tamara Hershey, Allison Cato, Peiyao Cheng, Craig Kollman, Roy W Beck, Katrina Ruedy, Tandy Aye, Larry Fox, Ana Maria Arbelaez, Darrell Wilson, Michael Tansey, William Tamborlane, Daniel Peng, Matthew Marzelli, Karen K Winer, Allan L Reiss, Diabetes Research in Children Network (DirecNet), Eva Tsalikian, Michael J Tansey, Julie Coffey, Joanne Cabbage, Sara Salamati, Amy Conrad, Nelly Mauras, Larry A Fox, Ellison Cato, Kim Englert, Kaitlin Sikes, Tina Ewen, Bruce A Buckingham, Darrell M Wilson, Tandy Aye, Kimberly Caswell, Kristin Schleifer, Christian Ambler, Stuart A Weinzimer, William V Tamborlane, Amy Steffen, Kate Weyman, Melinda Zgorski, Jodie Ambrosino, Neil H White, Ana Maria Arbelaez, Lucy Levandoski, Angie Stames, Tamara Hershey, Sarah June Grafeman, Roy W Beck, Katrina J Ruedy, Craig Kollman, Peiyao Cheng, Beth Stevens, Kelly Njeru, Ryan Chapman, Thomas Mouse, Allan L Reiss, Naama Barnea-Goraly, Matthew J Marzelli, Paul M Mazaika, Daniel X Peng, Tamara Hershey, Allison Cato, Emily Bihun, Amal Al-Lozi, Allison Bischoff, Michaela Cuneo, Aiden Bondurant, Mark Sperling, Dorothy M Becker, Patricia Cleary, Carla Greenbaum, Antoinette Moran

Abstract

Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA1c performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1
Figure 1
Longitudinal brain growth. Brain regions where the T1D group had significantly reduced growth compared with control subjects. A: Growth rate of total gray matter volume decreased with age (P < 0.001) and was significantly smaller for the diabetic group (red dots) vs. control subjects (black dots). P < 0.001. B: Regions of gray matter with significantly less growth for T1D than control subjects (P < 0.001). C: Regions of white matter with significantly less growth for T1D than control subjects (P < 0.001). B and C are subtraction images, so the more orange in a region, the less growth in the T1D group compared with the control group. L, left; R, right; yr, years.
Figure 2
Figure 2
Effects of dysglycemia with different brain regions. Brain regions where reduced growth in the T1D group was correlated with glycemic exposure over the 18 months of study. A: Gray matter regions where growth was negatively correlated with average MAGE (P < 0.001). B: White matter regions where growth was negatively correlated with average MAGE (P < 0.001). C: Gray matter regions where growth was negatively correlated with high glycemic exposure (difference in HbA1cAUC6%; P < 0.001). L, left; R, right.

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