Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children

Abstract

Objective: To investigate the impact of new-onset diabetic ketoacidosis (DKA) during childhood on brain morphology and function.

Research design and methods: Patients aged 6-18 years with and without DKA at diagnosis were studied at four time points: <48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients underwent magnetic resonance imaging (MRI) and spectroscopy with cognitive assessment at each time point. Relationships between clinical characteristics at presentation and MRI and neurologic outcomes were examined using multiple linear regression, repeated-measures, and ANCOVA analyses.

Results: Thirty-six DKA and 59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral white matter showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal, and parietal white matter. Total white matter volume decreased over the first 6 months. For gray matter in DKA patients, total volume was lower at baseline and increased over 6 months. Lower levels of N-acetylaspartate were noted at baseline in the frontal gray matter and basal ganglia. Mental state scores were lower at baseline and at 5 days. Of note, although changes in total and regional brain volumes over the first 5 days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months. Age at time of presentation and pH level were predictors of neuroimaging and functional outcomes.

Conclusions: DKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term.

Figure 1

Group differences (DKA vs. non-DKA) for TBVs. Data are presented as the estimated mean and 95% CI at each time point. A: Total supratentorial brain volumes. B: Total supratentorial white matter volume. C: Total supratentorial gray matter volume; *P = 0.014. D: Total cortical white matter volume/TBV; *P = 0.008. E: Total cortical gray matter volume/TBV; *P = 0.008.

Figure 2

Group differences (DKA vs. non-DKA) for frontal lobe volumes, diffusivity, and spectroscopy. Data are presented as the estimated mean and 95% CI at each time point. A: Frontal lobe white matter relative volume; *P = 0.002. B: Frontal lobe white matter diffusivity; *P < 0.001. C: Frontal lobe white matter NAA spectroscopy; *P = 0.005. D: Frontal lobe gray matter relative volume. E: Frontal lobe gray matter diffusivity; *P = 0.013. F: Frontal lobe gray matter NAA spectroscopy; *P = 0.005.

Figure 3

Group differences (DKA vs. non-DKA) for cognitive outcomes. Data are presented as the estimated mean and 95% CI at each time point. A: Mental state (SYSTEMS) score; *P = 0.002. B: Delayed memory raw score; *P = 0.002. C: Focused attention (Sky Search) scaled score. D: Dual-modality divided attention (Sky Search DT) scaled score. E: Single-modality divided attention (Score DT) scaled score. F: Sustained attention/impulsivity (Walk/Don’t Walk) scaled score. DT, dual task.