Severity of clinical presentation in youth with type 1 diabetes is associated with differences in brain structure

Abstract

Objective Differences in cognition and brain structure have been found in youth with type 1 diabetes compared to controls, even after relatively short disease duration. To determine whether severity of clinical presentation contributes to these differences, we obtained structural MRI scans in youth ages 7–17 who were either newly diagnosed with type 1 diabetes (<3.5 months from diagnosis, n=46) or a sibling without diabetes (n=28). Research Design and Methods Severity of presentation was measured by the presence of diabetic ketoacidosis (DKA) and degree of hyperglycemia exposure (hemoglobin A1c (HbA1c)) at diagnosis. Magnetic resonance images were obtained using T1-weighted, T2-weighted, and Diffusion Weighted sequences. Results Within the group with type 1 diabetes, 12 subjects presented in DKA, and 34 did not. After controlling for age, sex and multiple comparisons, the type 1 diabetes group had lower volume in the left temporal-parietal-occipital cortex compared to controls. Within the type 1 diabetes group, DKA at presentation was associated with lower radial, axial and mean diffusivity throughout major white matter tracts and higher HbA1c was associated with lower hippocampal, thalamic, and cerebellar white matter volumes, lower right posterior parietal cortical thickness and greater right occipital cortical thickness. Conclusion These data suggest that severity of clinical presentation is an important factor in predicting brain structural differences in youth with type 1 diabetes approximately 3 months after diagnosis.

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis

“…1–3,22–24 Subtle brain injury often occurs during treatment for diabetic ketoacidosis in children and may contribute to cognitive decline. 4–9 Excessive fluid administration, which may result in rapid osmotic changes, has been widely suspected to cause brain injury, 11,25,26 but a more recent hypothesis suggests that cerebral hypoperfusion and the effects of reperfusion, along with neuroinflammation, are central to diabetic ketoacidosis–related brain injury. 2,27–29 The latter hypothesis is consistent with reports that document symptomatic and even fatal brain injury occurring before the initiation of treatment for diabetic ketoacidosis.…”

“…1–3 Among patients without obvious neurologic decline during treatment for diabetic ketoacidosis, subtle neurologic alterations are often present after recovery, including deficits in memory, attention, and IQ 4–7 and changes in cerebral microstructure. 4,8,9 …”

Prefronto‐temporal white matter microstructural alterations 20 years after the diagnosis of type 1 diabetes mellitus

“…Similarly, previous studies provide supporting evidence that the structural and neurometabolic alterations related to T1DM, which is usually diagnosed during childhood, may be prominent particularly in the fronto‐temporo‐parietal regions . Considering the well‐known microvascular alterations of white matter (WM) in prolonged hyperglycemic conditions, it is important to focus on the fronto‐temporo‐parietal WM regions in investigating T1DM‐related brain structural abnormalities …”

“…In this study, we examined fractional anisotropy (FA), a sensitive marker for microstructural alterations in WM integrity, in both young adults with T1DM as well as healthy individuals using diffusion tensor imaging (DTI). We expected to observe T1DM‐related deficits in the fronto‐temporo‐parietal WM regions . In addition, we focused on the working memory domain as a neurocognitive substrate of T1DM‐related fronto‐temporo‐parietal WM deficits, considering its significant role in memory‐related processes .…”

Histological and cognitive alterations in adult diabetic rats following an episode of juvenile diabetic ketoacidosis: Evidence of permanent cerebral injury

“…[2,7,17] Magnetic resonance imaging studies have demonstrated changes in cerebral microstructure associated with DKA in children. [22] In addition, previous data from studies by our group have shown that DKA acutely causes reactive astrogliosis and activation of microglia in the brains of juvenile rats and that these findings are most prominent in the hippocampus. [17] The current data extend these findings to demonstrate that reactive astrogliosis does not resolve after DKA recovery but instead results in permanent alterations in hippocampal microstructure.…”