Type 1 diabetes mellitus (T1DM) is typically diagnosed in childhood and over time can lead to complications affecting the retina, heart, kidneys, peripheral nerves, and more recently appreciated, the brain. During childhood, the brain undergoes significant structural and functional changes and has a high and rapidly changing metabolic demand; these unique properties have led to the suggestion that the developing brain may be especially vulnerable to glycemic extremes. Accordingly, studies find that early age of onset, accumulated exposure to hyperglycemia and repeated severe hypoglycemia during development are associated with lower cognitive performance and altered brain structure in children with T1DM. Intriguing patterns have been identified, yet substantial individual variability in brain outcomes remains unexplained. More recently, our data and others' have suggested that clinical severity at diagnosis, particularly at younger ages, may contribute to cognitive and brain outcomes, even many years later. However, previous studies have not been designed to differentiate the effects of initial clinical presentation from the cumulative effects of subsequent glycemic extremes on the brain. Thus, the goal of this study is to determine how clinical features at the time of T1DM diagnosis shape the developmental trajectory of the brain and its responses to subsequent glycemic control. We propose to test this hypothesis explicitly by performing sensitive neuroimaging, cognitive testing and quantitative clinical measures on children with T1DM and their non- diabetic siblings at diagnosis and at 3 and 21 months post-diagnosis. Findings may highlight the need for programs aimed at early diagnosis of the disease, DKA prevention, and ?-cell preservation, particularly in at- risk youth, in order to minimize long-term negative consequences for brain health and development. Although recent exciting developments raise the possibility of better glycemic control using closed-loop insulin delivery systems or of curing T1DM through ?-cell transplants, the risks associated with clinical presentation of T1DM would still remain and need to be better understood.
Type 1 diabetes mellitus (T1DM) is typically diagnosed in childhood and over time can lead to complications affecting the retina, heart, kidneys, peripheral nerves, and more recently appreciated, the brain. Studies consistently find that early age of onset and, to a more variable extent, poor glycemic control over years are associated with reduced cognitive performance and altered brain structure in children with T1DM. As yet, our understanding of why early age of onset would pose more risks for the brain is limited, making interventions difficult to develop. Given that the initial clinical presentation of T1DM in childre is the earliest and often the most severe glycemic state they experience over their lifetime, it is possible that age of onset and severity of initial clinical presentation interact to modify risks fr brain health and development. This hypothesis has clear clinical implications and the potential to resolve conflicting literature, yet has not been explicitly tested. Thus, the goal of this studyis to determine how clinical features at the time of T1DM diagnosis, such as hyperglycemia, diabetic ketoacidosis (DKA) and degree of beta cell failure, interact with age of onset to shape the development of the brain and its responses to subsequent glycemic control.
| Siller, Alejandro F; Lugar, Heather; Rutlin, Jerrel et al. (2017) Severity of clinical presentation in youth with type 1 diabetes is associated with differences in brain structure. Pediatr Diabetes 18:686-695 |
| Kirchhoff, Brenda A; Jundt, Dustin K; Doty, Tasha et al. (2017) A longitudinal investigation of cognitive function in children and adolescents with type 1 diabetes mellitus. Pediatr Diabetes 18:443-449 |
| Semenkovich, Katherine; Bischoff, Allison; Doty, Tasha et al. (2016) Clinical presentation and memory function in youth with type 1 diabetes. Pediatr Diabetes 17:492-499 |
| Cato, Allison; Hershey, Tamara (2016) Cognition and Type 1 Diabetes in Children and Adolescents. Diabetes Spectr 29:197-202 |
| Semenkovich, K; Patel, P P; Pollock, A B et al. (2016) Academic abilities and glycaemic control in children and young people with Type 1 diabetes mellitus. Diabet Med 33:668-73 |
| Antenor-Dorsey, Jo Ann V; Meyer, Erin; Rutlin, Jerrel et al. (2013) White matter microstructural integrity in youth with type 1 diabetes. Diabetes 62:581-9 |
| Kirchhoff, B A; Lugar, H M; Smith, S E et al. (2013) Hypoglycaemia-induced changes in regional brain volume and memory function. Diabet Med 30:e151-6 |
| Arbelaez, Ana Maria; Semenkovich, Katherine; Hershey, Tamara (2013) Glycemic extremes in youth with T1DM: the structural and functional integrity of the developing brain. Pediatr Diabetes 14:541-53 |
| Hershey, Tamara; Lugar, Heather M; Shimony, Joshua S et al. (2012) Early brain vulnerability in Wolfram syndrome. PLoS One 7:e40604 |
| Perantie, Dana C; Koller, Jonathan M; Weaver, Patrick M et al. (2011) Prospectively determined impact of type 1 diabetes on brain volume during development. Diabetes 60:3006-14 |
Showing the most recent 10 out of 14 publications
