Project Summary Children with type 1 diabetes (T1D) suffer from subtle cognitive impairments and structural alterations in the brain. These impairments progress with age and may eventually lead to increased difficulty managing the disease, resulting in worsening glycemic control, potentially life-threatening complications, and reductions in quality of life. Causes of cognitive decline in T1D are not well understood. Episodes of hypoglycemia, chronic hyperglycemia, glycemic variability and diabetic ketoacidosis (DKA) have all been suggested to play roles. Our team at the University of Colorado proposes to join a multicenter NIH consortium to investigate the impact of T1D on neurocognitive and psychosocial functioning in pre-pubertal children. We propose collaborative development of the study protocol, enrollment of a representative study population, and prospective follow-up to collect exposure and outcomes data for hypothesis testing. This study will further elucidate the role of DKA, chronic hyperglycemia, severe hypoglycemia and established or emerging treatment modalities on neurocognitive and psychosocial functioning of pre-pubertal children followed for up to three years after T1D diagnosis. We propose to test the following hypotheses: H1: DKA at diagnosis of T1D has a detrimental long-term effect on neurocognitive and psychosocial functioning (including full scale IQ), independent of sex, race/ethnicity, and socioeconomic status. H2: Chronic hyperglycemia exposure, assessed by repeatedly measured HbA1c or CGM time above range (TAR >250), has a detrimental long-term effect on neurocognitive and psychosocial functioning, independently of sex, race/ethnicity, and socioeconomic status of the child. H3: Recurrent severe hypoglycemia or excessive time below range (TBR <70 mg/dl) has a detrimental long-term effect on neurocognitive and psychosocial functioning, independently of sex, race/ethnicity, socioeconomic status, and glycemic control assessed by HbA1c or time in range (TIR 70-180). H4: Routine vs occasional use of CGM has a protective long-term effect on neurocognitive and psychosocial functioning, independently of sex, race/ethnicity, and socioeconomic status of the child and average HbA1c. The proposed studies will help to further understand the impact of DKA, hyperglycemia, hypoglycemia, and current diabetes management modalities on the developing brain, including neurocognitive and psychosocial functioning.