Neurological Consequences of Diabetic Ketoacidosis at Initial Presentation of Type 1 Diabetes in a Prospective Cohort Study of Children

Abstract

OBJECTIVETo investigate the impact of new-onset diabetic ketoacidosis (DKA) during childhood on brain morphology and function.RESEARCH DESIGN AND METHODSPatients 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.RESULTSThirty-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.CONCLUSIONSDKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term.

Hyperketonemia (Acetoacetate) Upregulates NADPH Oxidase 4 and Elevates Oxidative Stress, ICAM-1, and Monocyte Adhesivity in Endothelial Cells

“…Several studies have also shown that diabetes associated ketoacidosis can cause cerebral edema, hemorrhagic stroke, or acute ischemia leading to intracerebral complications [16,17]. Recent studies using MRI measures show altered brain structure and injury associated with adverse neurocognitive outcomes including impairment in neuronal function and viability in T1D children [18,19]. Ketosis mediated cerebrovascular endothelial dysfunction has been shown to be associated with intracranial microvascular complications [20].…”

Age of Childhood Onset in Type 1 Diabetes and Functional Brain Connectivity in Midlife: Erratum

“…Later in life, declines in FA are associated with progression of aging in healthy populations (22). Alterations in FA have been seen in patients with T1DM (23,24), and alterations in MD have been associated with diabetes complications (25). Thus, in addition to functional ICN strength, measures of FA and MD can provide additional information on the structural alterations that may coincide with altered ICN activity.…”

Children with type 1 Diabetes Mellitus: access to special immunobiological and child care

“…In world terms, the occurrence of T1DM in children is expressive and its incidence has been increasing around 3% per year (2)(3)(4)(5)(6) . This disease can present long-term complications, and is the cause of high morbidity and mortality with impacts on the quality of life and increasing healthcare costs requiring interdisciplinary interventions, comprehensive care, health education, monitoring/follow-up checkups, surveillance, and rational and efficient use of available technologies (7)(8) .…”

“…Access to services and integration of health care are also fundamental and constitute challenges for organizing health care for these children, being common situations in the Brazilian reality (5)(6)9) . In Primary Health Care (PHC), basic actions for the child focus on monitoring growth and development, immunization, breastfeeding, healthy eating, accident prevention and attention to diseases prevalent during childhood, taking into consideration that family participation and partnership with health and community services are essential (10)(11) .…”

“…Families with children affected by T1DM face daily challenges in maintaining adequate blood glucose levels, preventing complications, continuing treatment and increasing knowledge about disease management (5)(6) . Access to services and integration of health care are also fundamental and constitute challenges for organizing health care for these children, being common situations in the Brazilian reality (5)(6)9) .…”