White Matter Structural Differences in Young Children With Type 1 Diabetes: A Diffusion Tensor Imaging Study

Abstract

OBJECTIVETo detect clinical correlates of cognitive abilities and white matter (WM) microstructural changes using diffusion tensor imaging (DTI) in young children with type 1 diabetes.RESEARCH DESIGN AND METHODSChildren, ages 3 to <10 years, with type 1 diabetes (n = 22) and age- and sex-matched healthy control subjects (n = 14) completed neurocognitive testing and DTI scans.RESULTSCompared with healthy controls, children with type 1 diabetes had lower axial diffusivity (AD) values (P = 0.046) in the temporal and parietal lobe regions. There were no significant differences between groups in fractional anisotropy and radial diffusivity (RD). Within the diabetes group, there was a significant, positive correlation between time-weighted HbA1c and RD (P = 0.028). A higher, time-weighted HbA1c value was significantly correlated with lower overall intellectual functioning measured by the full-scale intelligence quotient (P = 0.03).CONCLUSIONSChildren with type 1 diabetes had significantly different WM structure (as measured by AD) when compared with controls. In addition, WM structural differences (as measured by RD) were significantly correlated with their HbA1c values. Additional studies are needed to determine if WM microstructural differences in young children with type 1 diabetes predict future neurocognitive outcome.

Risk Factors for Decline in IQ in Youth With Type 1 Diabetes Over the 12 Years From Diagnosis/Illness Onset

“…However, our neuroimaging findings 12 years after disease onset (9) showed reduced volumes in the thalamus, a brain structure critical for arousal and vigilance, in those who had experienced a hypoglycemic seizure. Furthermore, the compromised white matter integrity demonstrated in recent DTI studies (4,6,12) is likely to degrade efficient processing of incoming information. Language development is highly sensitive to environmental input, particularly educational experience, thus subtle compromise of attention and information processing skills may lead to cumulative deficits in verbal knowledge stores over childhood.…”

“…There is a growing literature documenting pathophysiological CNS changes (4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and neurocognitive deficits (14)(15)(16)(17)(18)(19)(20)(21)(22)(23) in youth with type 1 diabetes. However, attempts to identify specific diabetes-related risk factors for CNS compromise have produced inconclusive findings.…”

Relationships of DTI findings with neurocognitive dysfunction in children with Type 1 diabetes mellitus

“…Upon arrival, the blood glucose levels of subjects were measured from their fingertip blood by their own manual device before MRI examination or neurocognitive testing. To standardize the study, subjects with blood glucose levels between 100 and 250 mg dl 21 were taken into our routine study protocol. We know that hypoglycaemia or hyperglycaemia may lead to acute diffusion changes in the brain and alter neurocognitive situation; therefore, subjects with glucose levels outside of this range were re-evaluated after 1 h or were given an appointment for another day again.…”

“…[19][20][21][22][23] To standardize the measurements, all regions of interest (ROIs) were obtained from the left side. T 1 weighted three-dimensional magnetizationprepared rapid-acquisition gradient-echo and T 2 w images were used as anatomic references for the placement and tracing of ROIs.…”

“…The mean duration of disease was 3.3 6 2.5 years, mean HbA1c value was 8.9 6 2.4 mg dl 21 and average onset age of the disease was 9.2 6 3.1 years. 15 patients with Type 1 DM had a history of DKA attack, and other 9 patients had a history of hypoglycaemia attack.…”